IEEE Biomedical News

• Under-Skin Implant Controls Prosthetic Arms

  

  Two patients in Melbourne, Australia, recently became the first recipients of a novel type of implant for controlling prosthetic arms. The 2-by-10-centimeter device, produced by Phantom Neuro, wraps around the forearm underneath the skin, where it measures electrical signals in muscles, a process called electromyography (EMG). That signal is then processed and translated into robotic commands for third-party prostheses.

  Options to control powered prosthetic devices that are currently available or in development look for signals from the brain, peripheral nerves, or muscles. Some methods also use a form of EMG, but inject probes deep into muscle. Surgeries to implant brain-based sensors can be even more invasive. Non-invasive approaches are commonly used, but often have their own drawbacks in reliability, comfort, or convenience.

  “The goal with this tech is to give amazing control, but with outpatient [care] more like a cosmetic procedure than brain surgery,” says Connor Glass, founder and CEO of Phantom Neuro, which is based in Austin, Texas. He describes the surgery as creating a pocket under the skin, comparable to common cosmetic implant procedures. Removal, when needed, is expected to be simpler than implantation.

  The company announced the successful procedures today, 20 October, about five months after the first took place. This is the first progress announced in an early feasibility trial in humans to assess the implant’s safety, which was approved by Australian regulators in April.

  Michael Easy sits with Phantom Neuro CEO Connor Glass while testing the implant.Shane Benson

  A Promising First Procedure

  Michael Easy, a 32-year-old carpenter from Hastings, Victoria, near Melbourne, was the first implant recipient. “It was a bit sore and tender for the first couple of days, and then it healed so quick, there was no drama whatsoever,” he says in statements relayed by Phantom Neuro. Easy also reports he experienced some swelling for two weeks post-operation.Easy was under operation for around an hour with mild sedation, and the entire process took about four hours. The second participant’s procedure was faster: It took around 45 minutes, notably did not use general anesthesia, and had the patient in and out of the hospital in three hours. Neural implant procedures can take many hours.

  The Phantom implant includes two rows of electrodes embedded in flexible medical silicone, with a disk of electronics at one end to process and send a wireless signal. A coil in the center is used for power delivery from an external source, similar to how a cochlear implant is powered.

  What works for one or two patients may not work for everyone, but aspects of early performance have been promising. For example, muscle signals have been strong and consistent, Glass says, and calibration between intent and gesture may last months, compared to the daily recalibration required with some surface EMG. “This implant has made everything easier and smoother and faster,” Easy says.

  Prosthesis control experts saw promise in the concept and form factor, but hoped for more public technical information and emphasized that at such an early stage of clinical research, many aspects of the device remain to be proven. “I see a tremendous potential benefit for patients to use every day more reliably,” says Helen Huang, a biomedical engineer at North Carolina State University in Raleigh and at the University of North Carolina in Chapel Hill.

  “Ultimately, these potential advantages must translate into tangible benefits for users, including more natural and reliable prosthetic control, reduced effort, and improved performance in daily activities,” says Loredana Zollo, a biomedical engineer at the Università Campus Bio-Medico di Roma, in Rome, Italy.

  Why Phantom Neuro Goes Under the Skin’s Surface

  Costs and benefits will in part be compared to the relatively common surface EMG approach. Surface electrodes sit on top of the skin and can be finicky when placed slightly off the target location, and the user’s sweat can change the impedance or cause them to shift on the skin. They may be uncomfortable as they dig into skin, and motion tends to create data artifacts. All of these issues can be made worse by physical activity.

  Michael Easy demonstrates using the implant in daily life while discussing his experience with CEO Connor Glass. Phantom Neuro

  Phantom Neuro’s under-the-skin approach offers a potentially more reliable alternative, but presents its own engineering challenges, Glass says. The implant must be able to withstand minor impacts from daily activity and maintain connection with an external power source despite movement of the arm and skin. The company also designed it to be compatible with a wide range of commercially-available prostheses, which do not have standardized communication protocols.

  Phantom’s current implants use machine learning to associate muscle signals with specific gestures or movements and can perform the same action at different speeds. But the implant cannot yet combine motions, such as wrist rotation and finger movement, and requires step-by-step motions to achieve some tasks. A long-term goal is to use more sophisticated pattern recognition to achieve what Glass calls “simultaneous proportional control.”

  Glass is hopeful that in two to three years, clinical trial progression will lead to FDA approval for upper limb prosthesis control, after which the company may pursue other commercial applications or patient groups. Phantom is already starting to look into some of these, including medical applications in lower limb prostheses, which are particularly challenging. (No commercial systems that use EMGare yet available.) Phantom is also exploring general augmentation and human-machine interactions in defense settings.

• World’s First Fully Implanted Cochlear Implant Reaches Patients

  

  Cochlear implants have transformed the lives of hundreds of thousands of people around the world by restoring lost hearing. But externally worn sound processors outside the ear have long been a source of friction, limiting daily activities and exposing users to stigma. A new, fully implanted cochlear implant from Austrian company Med-El now offers the prospect of round-the-clock hearing without any visible sign.

  Since the 1980s, cochlear implants have been used to bypass damaged parts of the ear in people with severe-to-profound hearing loss. Conventional devices feature an external unit worn on the back of the ear that houses a microphone, sound processor, and battery. This unit converts incoming sounds into electrical signals that are transmitted wirelessly through the scalp to an electrode array in the cochlea—a spiral shaped structure in the inner ear that converts sound waves into neural signals.

  Med-El CEO Ingeborg Hochmair, who developed one of the first multichannel cochlear implants in the 1970s in collaboration with her husband Erwin, says the ambition to create a fully implantable device dates back to the 1970s, but was held back by microphone and battery technology. But after more than 15 years of development, on Tuesday the company launched the TICI Unico, the world’s first commercially available fully implanted cochlear implant (or TICI, Totally Implantable Cochlear Implant).

  The device has received European regulatory approval and the first four commercial implantations were carried out on the morning of the announcement, though it’s not yet available in the United States. The company says a clinical trial of the device with 30 patients found it provided “comparable” hearing performance to Med-El’s conventional implants, while allowing users to hear while asleep, swimming, and recharging.

  “For the first time, all components of a cochlear implant, including the microphone, are implanted beneath the skin. There are no external components to wear, to remove, or to manage,” Hochmair said in a press conference. “This is the realization of a dream that I’ve had for a very long time. For the first time, invisible hearing with a cochlear implant is possible.”

  How the Fully Implanted Cochlear Implant Works

  The implant weighs 20 grams and is made up of four interconnected components. A subcutaneous microphone the width of a U.S. nickel, or a 5 euro-cent coin, sits roughly 6 millimeters beneath the skin of the scalp and connects to a postage-stamp-size “stimulator” unit that houses both sound processing hardware and a rechargeable lithium-ion battery. This is connected to a coil that’s used to transfer data in and out of the device and recharge the battery. Another lead passes signals to the electrode array in the cochlea, which is the same as the ones used in the company’s conventional devices.

  The unit is recharged using a car-key-size unit called a GoPod, which attaches magnetically to the charging coil through the scalp. The battery, which cannot be replaced, is designed to last for up to 40 hours on a single charge of about 1 to 1.5 hours. The company says performance data suggests it will be able to maintain a minimum of 24 hours of use per charge for at least 15 years.

  Bringing the microphone inside the scalp presented by far the greatest engineering challenge, said Gerhard Mark, senior R&D engineer at Med-El and project leader for the TICI Unico. “Sound behaves differently when it travels through the tissue, so reaching the performance required years of research, testing, and continuous refinement,” he said, though he declined to provide details on how the company solved the problem.

  How Does the Invisible Cochlear Implant Perform?

  So far, clinical results suggest the device can provide comparable performance to a conventional cochlear implant, said Philippe Lefebvre, head of the ENT department at University Hospital of Liège, in Belgium, who led a six-patient feasibility study on the implant published in Communications Medicine last year. Hochmair added that other studies have found the same, though that data is still awaiting peer review.

  Lefebvre said he had expected the invisibility of the device to be the biggest selling point for users, but in reality the ability to hear around the clock was the main benefit they cited. This was echoed by Diana Grosser, a volunteer who received a TICI Unico in 2024 as part of the clinical trial. “The most meaningful change is freedom,” she said. “I can sometimes forget that I’m deaf, live more freely with my children, swim or ride my motorcycle without worrying about my processor pressing, slipping, or getting lost. I can even choose to hear at night, which gives me additional safety.”

  Fan-Gang Zeng, director of the center for Hearing Research at the University of California, Irvine, said, “I applaud Med-El’s launch of this long-overdue device, which not only represents the first meaningful innovation in cochlear implants in the past 30 years since electroacoustic stimulation, but also accelerates the competition that the market desperately needs.”

  Zeng, who is not affiliated with Med-El, argues that industry conservatism has been a greater barrier than technical challenges and hopes that a first-mover will push other companies to release similar products soon.

• Tech to Replace Animal Testing Is Almost Ready. Scientists Are Not

  

  Seventeen years ago, cell biologist Donald Ingber and his colleagues at Harvard University’s Wyss Institute for Biologically Inspired Engineering submitted a paper to the journal Science describing their model human lung. It was smaller than a USB stick and made of a clear polymer slab containing narrow channels, which were lined with the type of cells that line a lung’s air sacs and blood vessels. When air was pumped through hollow chambers beside the channels, the device rhythmically expanded and contracted—it “breathed.”

  This lifelike movement was a dramatic change from previous generations of lung models, which typically used static cultures of lung tissue that were unable to simulate the movements essential to lung function. When exposed to inflammatory proteins and bacteria, Ingber’s artificial lung reacted much as living lungs would. And exposure to silica nanoparticles used to model the effects of ultrafine particulates revealed that movement affected how tissues absorbed them.

  Donald Ingber led the team that developed the first human lung-on-a-chip at Harvard University’s Wyss Institute.Sam Ogden

  It was a powerful proof-of-principle demonstration of a system that could be used to test drugs and other chemicals, providing a complement and even an alternative to testing in tissue cultures or in animals. Even so, the editors at Science were hesitant. They rejected the paper and suggested that Ingber’s team also run the tests in mice.

  It wasn’t an unreasonable request: Harvard’s lung system was new and comparing the results it generated to results from mice would help validate it. Ingber’s team ran the suggested experiments and resubmitted their study a year later, in 2010, at which point it was published. (It has since been cited by nearly 5,400 other papers.) Still, the incident spoke to how animal models have been the default of modern biomedical research.

  An early lung-on-a-chip developed at Harvard’s Wyss Institute used microfluidic channels lined with human cells to reproduce key features of lung function.Wyss Institute at Harvard University

  A recent story told by Ilka Maschmeyer, a translational toxicology researcher and executive at the German biotech company TissUse, shows how much things have changed. TissUse specializes in building organ-on-a-chip systems—the conversational name for systems like Ingber’s lung—that are used by pharmaceutical companies for research. A few months ago, says Maschmeyer, a pharmaceutical company approached TissUse after being denied permission by the U.S. Food and Drug Administration to run a clinical trial of a new drug. The problem: It had presented animal data, but the FDA wanted data from organs-on-a-chip or some comparable alternative. The standards had come full circle.

  A Breathing Lung-on-a-Chip

  

  The moment spoke to a trend, perhaps even the early days of a fundamental shift, away from the use of animals in toxicology and drug development. “It’s rare still,” says Maschmeyer, “but I think it’s going to be more and more frequent.”

  A host of these kinds of alternatives to experiments on animals have been developed over the years. Collectively they’re known as NAMs, an acronym that stands, depending on whom you’re talking to, for new approach methodologies, novel alternative methods, or nonanimal methods. Most NAMs have yet to be rigorously tested, but early studies suggest their potential.

  As NAMs have become more sophisticated, the question of how they will be implemented has become less about their technical qualities and more about the practical next steps needed to realize their potential. Validating NAMs—standardizing the systems, conducting head-to-head comparisons with animal experiments—is an enormous challenge. Moreover, simply outperforming animal models is necessary but not sufficient. The adoption of NAMs will require changes in policy, training, and culture.

  “This transition process is much more complicated than you would think,” says Thomas Hartung, a toxicologist and director of the Center for Alternatives to Animal Testing at Johns Hopkins University. “It is more about change management than it is about the technology.”

  The Technologies Replacing Animal Testing

  For decades, animal advocates and many scientists have criticized both the morality and usefulness of experimenting on animals. An estimated 92 percent of all drugs that enter U.S. clinical trials fail to reach the market, sometimes for business reasons but often because the drugs prove ineffective or unsafe in ways that were not predicted by animal experiments. Failure rates are even higher in drugs for heart disease, cancer, and diseases of the brain.

  These statistics don’t automatically mean that a reliance on animals is to blame. Flawed study designs are a problem too, and also the sheer confounding complexity of disease. But there’s little question that animals have made poor surrogates for many conditions. And just as animal experiments may mistakenly suggest efficacy or fail to predict harm in humans, they might also erroneously suggest that drugs are ineffective or harmful when they could actually work in humans. Some researchers argue that if aspirin or acetaminophen had been discovered after the advent of modern testing requirements, they might have been abandoned.

  

  

  TissUse’s Humimic systems use microfluidic chips to culture human tissues and model interactions between organs. A researcher images tissues in a chip during an experiment [top], Humimic chips sit in a temperature-controlled unit [center], and a researcher prepares chips for use [bottom].TissUse (3)

  Researchers developing NAMs have pushed these systems far beyond old-fashioned tissue cultures. The new technologies include organoids that more closely mimic the structure, composition, and function of human organs. More humanlike still are organ-on-a-chip systems; alongside Ingber’s lung-on-a-chip are brains, hearts, kidneys, and even placentas on a chip. As many as 10 such organs have been linked together, yielding multi-organ systems that promise to recapitulate many aspects of human physiology—not perfectly, but better than a mouse or a monkey would. Supporting these systems are computational simulations of organs and organisms, and also artificial intelligence tools that analyze data generated by other systems and inform future experiments in a high-powered iterative loop.

  Yet even as studies piled up and some pharmaceutical companies started using NAMs in-house, the U.S. regulatory system governing drug developing and testing remained an obstacle to their wider use. NAM proponents were overjoyed, then, when in late 2022 the FDA Modernization Act 2.0 passed into law. It explicitly authorized the use of NAMs in the preclinical studies required of new drugs before they could enter human trials. Previous regulations had mandated animal testing; now the door was open to alternatives. It was a landmark moment. “That was something I didn’t expect to see in my life,” says Maschmeyer.

  Although immediate in-the-lab impact was limited, the FDA’s decision was a harbinger of things to come. In 2025, the FDA pledged “to make animal studies the exception rather than the norm” for drug safety testing. Then, in September 2026, the agency followed up by issuing a rule that, if it takes effect, will replace references to “animal tests” in its drug-development regulations with the broader term “nonclinical tests.” The change makes explicit that validated alternatives such as human-cell systems, organs-on-chips, and computer models can be used when appropriate.

  Also in 2025, the U.S. National Institutes of Health, the world’s largest public biomedical research funder, announced that researchers applying for grants to study animal models would also need to incorporate nonanimal research, such as real-world data or studies of NAMs. Meanwhile, the European Commission and United Kingdom have announced their own plans to phase out animal testing, and the intergovernmental Organisation for Economic Co-operation and Development updated its influential guidelines to allow for expanded use of NAMs.

  NAM proponents say these shifts were essential: If regulators won’t accept NAM results, there’s less incentive to adopt them, especially for researchers already working with animals. Maschmeyer says TissUse’s clients increasingly include scientists whose research has been focused on animals. “I see, within the last year, a change,” says Maschmeyer. “It’s more people who are working with animal models who now have to also add in vitro models.” She traces it mainly to the regulatory shift—a trend Ingber calls “game-changing.”

  Proving That NAMs Work

  It’s not enough for regulators to say that NAMs can or should be used, though. Even more important is the regulatory apparatus dedicated to assessing how they should be used. This begins with their validation: the process by which experimental methodologies and devices are determined to be reliable and trustworthy. A prototype brain-on-a-chip designed to model a rare neurological disease might work fine in the lab that developed it—but to be validated, the system needs to work in the real world.

  “You read about all the organ chips that come out of academic labs, which is great—but that’s not going to change their uptake by the FDA, because you have to get the same results anywhere in the world. It has to be a commercial product. It has to be mass-produced and meet very fine performance criteria,” says Ingber. For example, even minute variations in the hydrogels used as tissue scaffolds in organ chips can produce very different growth patterns.

  Emulate’s Organ-Chips are connected to the company’s automated culture system, which supplies the chips with nutrients and controls the flow of fluid through them.Emulate

  Workflows and procedures need to be uniform, too. One obstacle to wider use of vascularized tumor-on-a-chip platforms in developing cancer therapies, for example, is the different metrics used by different research groups to characterize blood-vessel function and geometry. Experimental guidelines, workflows, checkpoints, metrics, reporting criteria: All need to be standardized in order for researchers to compare their work and collaborate across platforms. Members of Ingber’s lab coach industry researchers on how to use chips developed by Emulate, a company founded by Ingber. But even with instructions, they still need help with the finer points of tending to stem-cell cultures.

  When a NAM is ready for commercial use and researchers know how to use it, the most important test—whether it provides clinical benefit—still remains. A rare-disease organ chip might be reliable, but are the biomarkers it measures actually relevant? If so, are the algorithms that extrapolate chip results to the drug’s in-body effects truly predictive?

  

  

  Microscopic images reveal the human tissues grown inside Emulate’s Organ-Chips. Bacteria, shown in magenta, interact with mucus and airway cells in a LungChip [top]; an IntestineChip develops structures resembling those that absorb nutrients in the small intestine [center]; and tiny hairlike cilia grow on cells in another LungChip, where they help move mucus and trapped particles out of the airway [bottom].Emulate (3)

  Such questions have been answered for some NAMs. For example, a liver-on-a-chip system from Emulate correctly flagged about seven out of every eight drugs that had safely passed animal trials but proved toxic to human livers. A similar study was conducted by researchers from Oxford University and Janssen Pharmaceutica (later renamed Johnson & Johnson Innovative Medicine). That team showed that their computational simulations of human heart cells flagged compounds that caused a type of dangerous heart arrhythmia with 89 percent accuracy, compared to animal studies that were 75 percent accurate.

  Such studies, however, are complicated and costly. Emulate’s study required 870 chips and the labor equivalent of 16 full-time employees working for 16 weeks—efforts far beyond the reach of the average lab. If the researchers wanted regulatory approval to use their chip to predict large-molecule drugs rather than the small-molecule drugs they tested, they would have needed to run another such study for that particular use. And comparable studies ostensibly need to be conducted for every commercially available NAM and every context in which they would be used—a vast undertaking. “That’s a challenge,” says Kathy Archibald, founder of Safer Medicines Trust, a United Kingdom–based group that considers animals to be poor models of human biology. “It takes too long and costs too much, and small companies can’t afford to do it.”

  Ingber thinks that academic scientists need to collaborate more with industry researchers on NAMs, and that governments should fund those projects. He and other NAM proponents also stress the importance of having access to the necessary data: Without information from preclinical animal studies and human clinical trials, comparisons are difficult, but much of that data is now proprietary. Pharmaceutical companies and regulators need to share it, they say, and the FDA has called for an open-access repository of drug toxicity data. Hartung of Johns Hopkins also suggests that new animal experiments be run in parallel with NAMs, producing side-by-side comparisons.

  To Christian Maass, a computational biologist at the German biotechnology company ESQlabs, NAMS are overdue for a showdown with animal models. His company makes “digital twin” systems in which data from organ chip systems inform whole-human simulations of drug outcomes and disease progression. “I love what we are doing,” says Maass, speaking not only of his company but of the whole field. But he adds that researchers have not yet provided “the evidence and the proof that we are doing better or as good as the animal models.”

  Maass thinks that head-to-head comparisons are essential to good science. After all, if a NAM doesn’t outperform an animal model, or works best as a complement rather than a replacement, that needs to be known. He also believes such studies could convince skeptics. Maass mentions the debut of the iPhone, when people saw for the first time how well a phone could work without buttons. “That was an ‘aha!’ moment,” he says. But for NAMs, “that moment is still lacking.”

  Changing Scientific Habits

  Even when those head-to-head comparisons are made, though, and regulations are appropriately changed, adoption can be slow. In the mid-1990s, researchers developed and validated the monocyte activation test—an assay that uses human blood cells to predict immune response—to replace the rabbit pyrogen test, which involves injecting a compound into a rabbit’s ear and monitoring the animal’s rectal temperature. But it wasn’t until 2010 that the European Pharmacopeia—the official Europe-wide standards for such testing—accepted the monocyte activation test as a replacement. And rabbits are still widely used for this test worldwide.

  Why the slow pace of change? In part because updates to guidance documents referring to animal tests lagged behind, but also because of inertia within the culture and institutions of science. “The formal requirement may disappear, but the informal expectation persists,” says Kathrin Herrmann, a veterinary scientist and colleague of Hartung’s at the Center for Alternatives to Animal Testing. Regulators, grant reviewers, peer reviewers, journal editors—the human infrastructure of science—often still expect to see animal data and are unfamiliar with NAMs.

  Herrmann is now overseeing a survey of early-career researchers working with, or trying to make the switch to, NAMs. “We consistently hear concerns that NAM-only proposals are perceived as risky by funders, that there is pressure to ‘add an animal experiment’ for credibility, that access to NAM infrastructure is limited, and that career trajectories become uncertain when departing from established animal models,” says Herrmann.

  The vast majority of drugs entering clinical trials in the United States fail to reach FDA approval, with particularly high failure rates in some therapeutic areas.

  Animal models are embedded in databases, training programs, and the very culture of research. Scientists who use animals may be reluctant to change; their identities as researchers are tied to animals and, more practically, they’ve spent their careers learning the techniques. A toxicologist who has used rats for decades might understandably look askance when asked to take a chance on unfamiliar chunks of polymer and stem cells—especially when human well-being, or millions of dollars, may ride on the choice. Likewise, an academic scientist whose career was built on animal models may not welcome NAMs; a switch may represent the loss of jobs for lab members whose expertise is no longer relevant. “I could see why it’s a hard thing for people to take it up,” says Ingber.

  Education and training is vital, say NAM proponents. The NIH and FDA now offer resources for researchers interested in NAMs, as do their counterparts in other countries embracing the technologies. Herrmann helps run webinars where researchers and regulators learn to use and evaluate NAMs; Hartung’s modules on Coursera, the online learning platform, have been taken by about 12,000 students so far. “These trainees will set up their own labs. They will go to industry. They will replace the old guard,” says Joseph Wu, director of Stanford University’s Cardiovascular Institute.

  Wu is also a cofounder of Greenstone Biosciences, a company that uses stem-cell-derived human tissues and AI to model disease and predict drug responses. He’s used that position to introduce researchers to NAMs, helping convince the company’s directors to freely share Greenstone’s large library of stem-cell lines with any academic researchers who want to use them. “I really believe that people should understand how this platform works,” says Wu. “At the end of the day, we’re just trying to advance science.”

  With enough time—and funding, incentives, training, education, collaboration, and generational turnover—the research culture of drug development and safety testing may shift. Whether NAMs will be used in other areas of science, though, is an open question. Early-stage drug development and regulatory testing account for roughly 30 percent of animals used in experiments; the rest are used in basic biological research. Replacing those animals is less straightforward, but it may be possible: Ingber describes organ-on-a-chip-based insights into inflammatory bowel disease, preterm birth, and treating viral infections that couldn’t have been made in animals. Hartung calls the adoption of NAMs in toxicology a “lighthouse function,” helping guide the way for other types of research.

  “Suddenly, all the dams have opened,” he says.

• Lab on a Contact Lens Can Measure Stress Through Serotonin

  

  A “lab on a contact lens” can measure the neurotransmitter serotonin in tears, potentially offering a novel wearable method to noninvasively analyze levels of stress, a new study finds.

  “Tears could become a practical, noninvasive source of biochemical information that can be measured repeatedly over time,” says Yangzhi Zhu, director of the biomedical device center at the Terasaki Institute for Biomedical Innovation in Los Angeles. “Most biomarker testing today still relies on blood draws or isolated laboratory measurements, which provide only snapshots. A wearable platform based on a contact lens could eventually make it possible to follow biochemical changes more continuously and in everyday settings.”

  Stress is linked to the development of many disorders, such as depression and schizophrenia. Currently, doctors often measure stress using questionnaires or diaries, but these are highly subjective, complicating accurate evaluations. In the new study, researchers sought to create a device that measured serotonin for a potentially objective method to gauge stress.

  Serotonin, often called a “feel-good” hormone, plays a central role in regulating mood. It’s found mostly in the digestive tract, blood, and nervous system, but small amounts can also be found in tears. As such, the scientists explored whether tears might offer a noninvasive, easily accessible route to analyze serotonin levels. However, because serotonin is only present at very low concentrations, Zhu says, “a sensor needs to be extremely sensitive while still distinguishing serotonin from other molecules in tears.”

  Developing a smart contact lens

  Zhu and his team fabricated soft, reusable hydrogel lenses encapsulating flexible biocompatible graphene and silver electrodes printed in serpentine patterns designed to tolerate repeated deformation. A compound called ferrocene was bonded onto the graphene to help detect serotonin in a strong, repeatable manner.

  The researchers tested these smart contact lenses in lab dishes with commercially available artificial tears that they laced with serotonin. The lenses could detect as little as 72-trillionths of a mole per liter of serotonin, well below the average serotonin concentration in human tears of roughly 15-billionths of a mole per liter. Experiments also showed the lenses could withstand more than 28 days of repeated flipping, folding, stretching, and twisting while staying functional.

  The scientists also tested the lenses in lab dishes on tears collected from 10 volunteers five minutes before, immediately after, and roughly 30 minutes after they each performed a pair of stressful tasks—public speaking and math challenges. As expected, serotonin levels in tears fell with increased stress.

  In addition, the researchers placed one of their lenses on the eye of an anesthetized live pig for about five minutes. The lens could detect serotonin when the eye was given artificial tears containing 50 and 100 nanomolar levels of the hormone. In addition, the lens caused no sign of infection or irritation.

  “We were able to detect very low concentrations of serotonin in tears using a soft contact-lens platform while preserving the transparency, flexibility, and comfort-related properties of the lens,” Zhu says.

  When the lenses were used to detect serotonin in the lab and with the pig, the scientists connected the lenses to readout equipment using soft flexible nickel wires. Zhu and his colleagues have developed a proof-of-concept wireless version of their lens incorporating a miniaturized near-field communications (NFC) chip and stretchable antenna for battery-free sensing and smartphone-based data transmission. However, they say further optimization, safety testing, and validation are needed. (Corrective versions of these lenses could also be made, Zhu says.)

  Promise for noninvasive biosensing

  All in all, “I think the work highlights an exciting direction in wearable biosensing—moving beyond physical signals such as heart rate and temperature toward continuous monitoring of molecular information,” says Wei Gao, a professor of medical engineering at the California Institute of Technology who did not take part in this research. “The eye and tear fluid provide an interesting interface for this because they may enable repeated biochemical measurements without blood sampling.”

  In tests where the scientists limited the movements of mice for a few hours per day in order to increase their stress, the researchers found that serotonin levels dropped in both the rodents’ blood and tears to a similar degree. These findings suggest that tears may provide a noninvasive window into blood serotonin levels, but more testing is needed before doctors might use these lenses in medicine, Zhu says.

  “We need to understand how tear serotonin varies across different individuals, times of day, stress conditions, ocular surface states, and disease conditions, and how those measurements relate to blood biomarkers and clinical assessments,” Zhu says.

  The researchers also measured the stress hormone cortisol in the lab tests of the tears as they used the lenses to measure serotonin. A number of techniques are already being developed to monitor cortisol, such as patches measuring it in sweat or fluid under the skin. Zhu says measuring both serotonin and cortisol can provide complementary information—cortisol measures immediate, short-term responses to stress, while serotonin gives a picture of what a person faces in the long term. He adds that detecting serotonin is also more challenging and shows what they can do with their technology.

  In the future, the scientists would like to move beyond measuring only serotonin using their lenses, and to analyzing multiple molecules at the same time for “a much richer picture of a person’s physiological state,” Zhu says. “The long-term goal is to develop a comfortable, wearable platform that can track biochemical changes over time in everyday life.”

  The scientists detailed their findings 16 September in the journal Science Translational Medicine.

• Ingestible Paper Battery Powers Biodegradable Medical Devices

  

  Typically, if you swallow a battery, it’s a mistake that calls for a trip to the hospital. But that’s not the case with a new ingestible paper battery developed by scientists at MIT. The battery could be used to power medical devices inside the body before safely breaking down.

  In tests in live pigs, the paper battery “generated sufficient power to perform meaningful functions inside the gastrointestinal tract, including meter-scale wireless communication and continuous electrical stimulation over several days,” says Giovanni Traverso, a professor of mechanical engineering at MIT.

  Smart Pills and Ingestible Electronics

  There is a broader trend in healthcare to develop smart pills. These ingestible electronics can analyze and treat the body from within in real time. However, ingestible electronics need a safe and reliable source of power.

  Conventional alkaline or lithium-ion batteries can prove deadly if their protective casings leak inside a person. Previous research has sought to develop energy-harvesting techniques for ingestible electronics, but these usually generate low and inconsistent levels of power. Scientists have also designed biodegradable batteries, but these often can only store limited amounts of energy.

  Traverso and his colleagues developed a paper-based battery with electrodes made from magnesium and molybdenum trioxide, as detailed in a paper published 21 September in Nature Chemical Engineering. Prior work had explored both materials for use as biodegradable batteries but had used bulky adhesives to bind large particles of these materials into batteries, resulting in thick electrodes that took longer to break down.

  The new batteries instead use cellulose nanofibrils (essentially, paper) to bind the electrode materials to the battery. These fibrils are sturdy, can load electrode particles into their porous structures, and can be thin and biodegradable, Traverso says.

  Battery electrolytes—which help electric charges shuttle between a battery’s electrodes to discharge electricity—are often toxic. The new paper battery uses a biodegradable ionic liquid gel based on choline chloride and lactic acid as its electrolyte, which yielded more stable performance than several other biodegradable electrolyte approaches, Traverso says.

  “Encapsulation was also critical,” Traverso says. “If gastric fluid reached the battery too quickly, its capacity declined prematurely. If the encapsulation persisted for too long, the device would not degrade as intended. Natural wax coatings provided a way to delay fluid penetration and tune the operating lifetime.”

  Researchers developed bioresorbable electrodes for an ingestible paper battery. After 90 days under accelerated conditions, the electrode material has almost completely dissolved.Source images: Mehmet Girayhan Say, Ada Erus, et al.

  Paper Battery for Gastrointestinal Devices

  In tests in live pigs, the batteries generated a peak voltage of 1.84 volts and remained operational in the stomachs of the swine for up to three days. They could power an RFID tag in a pill that, after it was swallowed, maintained stable wireless communication with a receiver 1.5 meters away. Similar smart pills could theoretically help doctors track whether a patient has indeed taken prescribed medication. The batteries could also power a capsule that electrically stimulated the stomach for 20 minutes, an electroceutical technique used to treat gastrointestinal conditions involving impaired digestive function, nausea, or loss of appetite. There was no notable tissue damage from this stimulation. The RFID tag and the circuit board used for electrical stimulation was not biodegradable, but was naturally excreted.

  “The battery could potentially power ingestible sensors that measure temperature, pH, pressure, motility, or biochemical signals; systems that transmit physiological information; controlled drug-delivery devices; temporary electrophysiological recording systems; and gastric or intestinal electroceutical devices,” Traverso says. “It may be particularly valuable for devices designed to remain in the stomach for several days, because a bioresorbable power source could reduce or eliminate the need for retrieval.”

  The scientists are now prototyping devices that combine these new batteries with biodegradable antennas and RFID systems. The goal is a human clinical trial of a device that can monitor how well patients are taking medicine, “which we aim to start in about two years,” Traverso says.