Researchers have uncovered evidence that age-related genetic mutations commonly associated with cancer and blood disorders may also contribute to the chronic brain inflammation characteristic of Alzheimer’s disease.
In a study published in Cell, investigators from the Icahn School of Medicine at Mount Sinai and Boston Children’s Hospital identified somatic mutations in brain immune cells from patients with Alzheimer’s disease. The findings suggest that genetic alterations acquired during aging may reshape the behavior of these cells, driving inflammatory processes linked to neurodegeneration.
The work introduces a potential new biological mechanism connecting aging, immune dysfunction, and Alzheimer’s disease, a condition that affects millions of people worldwide and remains one of the leading causes of dementia.
Linking aging, immunity, and neurodegeneration
Inflammation has long been recognized as a central feature of Alzheimer’s disease. Activated immune cells are commonly observed surrounding amyloid plaques and other pathological hallmarks of the disease. However, the factors that initiate and sustain these harmful immune responses have remained incompletely understood.
The new study focused on microglia, the brain’s resident immune cells. These specialized cells play critical roles in maintaining neural health by clearing cellular debris, regulating synaptic connections, responding to injury, and coordinating immune activity within the central nervous system.
Previous research has shown that microglia can adopt disease-associated states during Alzheimer’s progression, but the molecular triggers responsible for these changes have been unclear.
“Our data suggest that some immune cells in Alzheimer’s disease undergo genetic changes over time that alter their behavior and potentially contribute to chronic inflammation in the brain,” said senior author Samuele Marro, PhD, associate professor in the Nash Family Department of Neuroscience and The Friedman Brain Institute at Mount Sinai.
“These findings provide a new framework for understanding how aging, immune dysfunction, and neurodegeneration may intersect in Alzheimer’s disease.”
Large-scale analysis of Alzheimer’s brains
To investigate whether acquired mutations might contribute to disease pathology, researchers analyzed 311 postmortem brain samples from individuals with Alzheimer’s disease and age-matched controls.
Using ultra-deep sequencing, the team screened 149 genes frequently associated with cancer and clonal hematopoiesis, an age-related condition in which blood stem cells acquire mutations that allow certain cell populations to expand disproportionately over time.
The analysis revealed significantly higher numbers of somatic mutations in Alzheimer’s disease brains compared with controls.
Several of the most frequently mutated genes, including TET2, DNMT3A, and ASXL1, are well-known drivers of clonal hematopoiesis and have previously been implicated in age-related blood disorders and cancer development.
Many of these mutations were highly enriched in microglia-like immune cells while being largely absent from neurons, suggesting that immune cells may be a primary target of these age-related genetic alterations.
Evidence for blood-derived immune cell involvement
The researchers also examined matched blood samples from some patients and found that many of the same mutations detected in the brain were present in circulating blood cells.
This observation suggests a possible route by which mutated immune cells originating from the blood may enter the brain and adopt microglia-like functions.
Growing evidence has indicated that peripheral immune cells can contribute to neuroinflammation under certain conditions. The new findings raise the possibility that age-related expansion of mutated blood cell clones could influence inflammatory processes within the brain.
Such a mechanism would provide a direct biological link between clonal hematopoiesis—an increasingly recognized consequence of aging—and neurodegenerative disease.
Functional effects of Alzheimer’s-associated mutations
To determine whether these mutations actively alter immune cell behavior, the researchers combined single-cell analyses with stem cell-based experimental models.
Using CRISPR gene editing, they engineered induced pluripotent stem cell-derived microglia-like cells carrying mutations identified in Alzheimer’s disease samples.
The resulting cells displayed profound changes in gene expression, adopting inflammatory programs and disease-associated microglial states that have previously been linked to neurodegeneration.
“Our study provides functional evidence that mutations commonly associated with aging blood cells and cancer biology can directly alter the behavior of brain immune cells,” said co-corresponding author Eirini Papapetrou, MD, PhD, professor of oncological sciences at Mount Sinai and director of the Center for Advancement of Blood Cancer Therapies.
“These mutated cells showed inflammatory signatures strongly associated with neurodegeneration.”
The findings suggest that these mutations are not merely bystanders but may actively influence cellular pathways involved in disease progression.
A potential new contributor to Alzheimer’s pathology
The study expands the growing view of Alzheimer’s disease as a disorder involving complex interactions between the immune system and the nervous system.
Historically, Alzheimer’s research has focused heavily on amyloid-beta plaques and tau tangles. More recently, attention has shifted toward the role of neuroinflammation and immune dysfunction as key drivers of disease progression.
The identification of somatic mutations in microglia-like cells adds another layer to this emerging picture. Rather than being solely inherited or environmentally driven, some aspects of Alzheimer’s pathology may arise from genetic alterations that accumulate naturally with age.
Because clonal hematopoiesis becomes increasingly common in older adults, the findings may have implications beyond Alzheimer’s disease and could influence understanding of other neurodegenerative disorders characterized by chronic inflammation.
Implications for future therapies
Although the study does not establish that these mutations directly cause Alzheimer’s disease, it identifies a plausible mechanism through which age-related genetic changes could exacerbate neurodegeneration.
Future studies will be needed to determine how early these mutations emerge, whether they predict disease risk, and whether interventions targeting mutated immune cell populations could slow disease progression.
“This work highlights a potentially important connection between aging blood biology and neurodegenerative disease,” said Marro.
“If confirmed in future studies, these findings could open new avenues for therapies that target harmful inflammatory immune cell populations in the brain.”
The researchers are now planning follow-up studies in animal models to further investigate the role of mutated immune cells in Alzheimer’s disease and evaluate whether reducing their inflammatory activity can modify the course of neurodegeneration.
Scientific publishing is facing a growing challenge from fabricated research produced by industrial-scale paper mills. But researchers and publishers are fighting back through technology and collaboration to protect the integrity of the scientific record.
Scientific publishing is based on the trust that the data are real and that peer review ensures quality. But that trust is being eroded by commercial enterprises known as paper mills—coordinated commercial operations that sell authorship slots in fraudulent or manipulated manuscripts, then submit those manuscripts to journals.
Unlike traditional misconduct, these are not lone researchers cutting corners but businesses producing research at scale, often tailored to meet the demands of specific fields, journals, and career incentives.
A recent analysis of almost 19,000 online adverts for paper mills revealed authorship slots being sold for between $36 to $5,600 depending on the position of the slot, highlighting how commercialized the market is. The average for a first author position was $1,030 and, although the study did not examine which adverts resulted in published papers, another investigation traced approximately 1,000 authorship adverts to more than 400 published papers.
The magnitude of the problem is difficult to estimate. A 2022 report by the Committee on Publication Ethics (COPE) and the International Association of Scientific, Technical & Medical Publishers (STM) found that the percentage of suspect papers submitted to journals was around two percent overall but increased sharply to as high as 46% in journals targeted by paper mills.
The pressure to publish
Adrian Barnett, PhD Professor Queensland University of Technology
For honest researchers, it might be difficult to understand why paper mills even exist. At the heart of the issue is what Adrian Barnett, PhD, a professor in the Australian Centre for Health Services and Innovation at Queensland University of Technology, described as the “publish or perish” phenomenon.
“If I could do one simple thing tomorrow, I would ban all the university league tables,” said Barnett. “They’re just encouraging corruption.” Ranking systems that prioritize publication volume can push researchers toward quantity over quality, making paper mills an easy way to meet expectations.
Furthermore, publication is often not just a measure of success but a requirement for career progression. “For the clients, it’s believed that they need publications that they can’t achieve through their own efforts, either because they don’t have the time, the facilities, the training, or the money to do research and yet, for whatever reason, their employers expect them to,” explained Jennifer Byrne, PhD, a professor of molecular oncology and lead of the Publication and Research Integrity in Medical Research group at the University of Sydney.
Jennifer Byrne, PhD Professor University of Sydne
Byrne has published extensively about paper mills and publication integrity; she got into the field accidentally when she came across some papers about a gene that her team discovered many years earlier. “In 2014–2015, we realized that five or six different groups suddenly published very similar papers about this gene in different journals,” she said. “And I just thought, that doesn’t really make a lot of sense.”
Upon investigation, Byrne found that the papers, and a further 48 similar publications, showed features consistent with mass production. She has since proposed that human gene research in general is highly vulnerable to paper mills. “You can hide fake research quite effectively in experimental fields, because it’s very difficult and time-consuming to reproduce experimental studies,” she said.
Why paper mills matter
Aside from the obvious fraud, paper mills are problematic for several reasons. Byrne describes them as “a billion-dollar problem” with few resources devoted to tackling it. And although she and others have advocated for scaled investments, progress so far has been slow.
The publishing system can also reinforce the problem. Paper mills are profit-driven, but journals also benefit through article processing charges and citations, creating what Byrne describes as a “circle” in which “everyone gets what they want.”
The consequences of paper mill papers being published can influence real research. The papers are cited, reused, and built upon, wasting both time and money for all involved.
More broadly, the erosion of trust can drive researchers away from entire fields. In Byrne’s case, she stopped doing preclinical cancer research. “I left because there were a lot of papers that I couldn’t trust. When you get to the point where you can’t trust most of the recent literature, it’s very difficult to continue,” she said.
There are also more sinister risks. Barnett recalled reports of paper mills exploiting their clients, including instances of potential blackmail. “If you’ve been a regular customer and then you suddenly stop, they might try and squeeze more money,” he said. “They’ve got absolutely no scruples.”
Despite these impacts, deterrents are limited. “There are almost none,” said Byrne.
Retractions are often slow, meaning damage is done before action is taken, and retraction rates are far below where they should be.
In an April 2026 report to a U.S. Congress hearing on the state of scientific publishing, Kate Travis, managing editor of Retraction Watch, showed that the retraction rate was around 0.2% in 2025, up from 0.02% in 2016. Yet, the report states that Retraction Watch “are confident that the rate […] should be about two percent—10 times what it is today.”
How to tackle the problem
Concerns about problematic papers are often raised by individual researchers or so-called science sleuths on platforms such as PubPeer. Although they have become skilled at spotting telltale signs of a paper mill, like manipulated images, distinct layouts, author affiliations that might not match the topic of the paper, unusual patterns of coauthors, and fake peer reviews, it is difficult for the untrained eye to detect problems from a single paper.
This is why there have been calls for increased awareness. “Awareness is always the first step,” said Byrne, who is working with The Lancet–World Conferences on Research Integrity Foundation commission to address critical issues related to research integrity.
Efforts to extend awareness are also being coordinated through initiatives such as United2Act, which brings together stakeholders from research institutions, publishers, sleuths, and universities to develop shared guidance and educational resources.
But even with greater coordination, human detection has limits. As paper mills scale, automated tools are becoming essential.
Earlier this year, Barnett, Byrne, and colleagues published a paper in the BMJ showing that their large language model (LLM) could flag papers suspected of being from paper mills by analyzing sentence-level patterns. The model identified 9.9% of more than 2.6 million cancer research papers for further review. Many of the papers were linked to regions with strong publication incentives, including China.
However, Barnett emphasized that the model “is not a 100% proof, it’s a quick and simple flag that should encourage reviewers to look at those papers and look for other signs of paper mill activity.”
Other paper mill detection technologies are also available. Platforms such as Clear Skies, which is used by the STM Integrity Hub, use machine learning to detect patterns across large bodies of literature, while image-forensics tools and cross-publisher data sharing help identify duplicated figures and submissions.
Alongside these tools, Barnett suggested that researchers may increasingly need to provide a “breadcrumb trail,” through preregistration of hypotheses and transparent workflows to demonstrate the authenticity of their work.
Platforms such as PubPeer and Retraction Watch also play a role, enabling researchers to flag concerns and share evidence about suspect papers after publication. These flags then prompt journal retractions and investigations, making it a critical component in the fight against paper mill activity.
A call for tighter regulation
Aside from technology, Byrne would like to see tighter regulation for the commercial publishing industry, akin to something like the ISO 9001 quality management standards that have been widely adopted across industries like manufacturing, engineering, and healthcare.
“We need a regulatory framework that rewards journals that do the right thing and that care about publishing quality,” she said. “And we need to disincentivize the current commercial drive towards publishing anything for money.”
Byrne believes that funders and researchers should be demanding these standards. “They pay for the research, the journal subscriptions, the article processing charges, and give their research for free,” she said. “They don’t ask anything in return, in terms of quality standards, and that’s unacceptable.”
Marie Soulière, PhD Elected Trustee COPE
Marie Soulière, PhD, an elected trustee of COPE and chair of the COPE Paper mill Working Group, acknowledged that “a standard such as ISO 9001 could help with process consistency, documentation, and accountability.” But she said, “it would not be a direct solution to publication fraud or paper mills” and “would need to sit alongside integrity-specific controls, not replace them.”
How publishers are responding
Publishers are increasingly shifting from isolated responses to coordinated action. Initiatives like the STM Integrity Hub and United2Act are driving cross-industry collaboration and shared detection approaches.
Soulière said that several recommendations from the COPE/STM 2022 “have been put into practice, particularly around cross-publisher collaboration, shared screening approaches, and investment in integrity infrastructure.”
A central strategy, highlighted in a publication from the United2Act working groups, uses the “Swiss Cheese Model,” a move toward layered screening that combines tools such as plagiarism screening, image forensics, citation analysis, and author verification. “Each safeguard has limitations, but multiple checks together make it harder for fraudulent papers to pass through,” said Soulière.
Adya Misra, PhD Associate Director Sage
Publishers are also strengthening internal processes. As Adya Misra, PhD, associate director of research integrity at Sage, described: “Our research integrity team acts centrally to support editors and internal journal teams with both prevention of suspicious or problematic research and the correction of the scholarly record … in line with COPE guidance.”
A spokesperson for Taylor & Francis highlighted their work on external collaborations designed to address the root causes of integrity issues. They are partnering with the National Science Library at the Chinese Academy of Sciences to develop research integrity and publishing ethics training programs, designed to ensure that students and researchers at all levels receive adequate support and to help them avoid exploitation by unethical third-party services such as paper mills.
AI changes the game
Even as safeguards improve, artificial intelligence (AI) is moving the goalposts. Many current detection strategies were developed to target structured forms of fraud; template-driven papers, recycled images, and repeated patterns across manuscripts. But these signals are beginning to disappear. “Our system worked because the paper mills would have a template, but now with AI, there is no template,” said Barnett. “It’s going to absolutely change everything.”
Barnett and his colleague Matt Spick, PhD, a lecturer in health and biomedical data analytics at the University of Surrey, recently demonstrated this by generating a complete scientific paper in just under 30 minutes using publicly available data and the OpenAI platform PRISM.
“All we did was give it the dataset and said write a paper for an Elsevier journal,” Barnett explained. “If an honors student had given me this paper, I would have been pretty pleased.”
Credit: Hispanolistic / Getty Images
Paradoxically, AI could also be bad news for paper mills as people realize they can create the papers themselves at little to no cost.
Reasons for cautious optimism
With AI adding to the challenges that publishers and researchers already face, the future could appear bleak. Barnett recalled an analogy describing the AI problem as an oil spill in a digital ocean, “We don’t know how deep it is, can’t get to the bottom of it, and it’s very difficult to clean up.”
Even removing a single problematic paper can require significant time and effort, while thousands more remain undetected. But Byrne remains positive that the work being done can have an impact.
“I’m actually really positive, because I think the biggest thing is awareness,” she said, noting that when she gives talks, she asks if the audience has heard of paper mills. “In 2023, that might have been five percent of people, and yet by 2025 it had increased to 30%–50%,” she said.
Soulière added that increased collaboration and transparency within scholarly publishing is another positive takeaway.
“Publishers, editors, institutions, and other stakeholders are no longer treating these issues as isolated problems,” she said. “They are investing in stronger screening systems, clearer policies, and better cross-sector coordination. In that sense, this moment is also driving progress and innovation.
“While the risks are serious, the response from the sector shows that trust can be reinforced, and that the system is becoming better equipped to detect problems earlier and protect the scholarly record more effectively,” Soulière concluded.
Laura Cowen is a freelance medical journalist who has been covering healthcare news for over 10 years. Her main specialties are oncology and diabetes, but she has written about subjects ranging from cardiology to ophthalmology and is particularly interested in infectious diseases and public health.
Researchers at Nagoya University, Japan, have developed a nanowire-based microfluidic device they say can improve the detection and analysis of cancer-associated extracellular vesicles (EVs) in blood samples. The new device uses zinc oxide nanowires modified with antibodies to selectively capture EVs linked to cancer while preserving both their surface proteins and internal microRNAs, which can then be analyzed. The findings, published in the journal Device, indicate that new device could potentially improve liquid biopsies for ovarian cancer as well as other cancers.
“In this study, we developed a nanowire microfluidic device capable of selectively capturing cancer-associated EVs with high efficiency, while suppressing nonspecific adsorption through simple chemical modification,” said senior author Takao Yasui, PhD, a professor in the graduate school of engineering at Nagoya University. “We also demonstrated that this approach maintains both EV membrane proteins and internal microRNAs intact, showing strong potential for highly sensitive analysis of cancer states.”
EVs are an emerging class of analytes because they carry molecular cargo such as messenger RNAs, microRNAs, and membrane proteins that reflect the cells from which they originate. To date, however, there have been challenges finding way to isolate EVs from complex biological fluids.
According to the researchers, techniques to isolate EVs such as ultracentrifugation, size-exclusion chromatography, and polymer-based precipitation can be time-consuming, require large sample volumes, and provide limited specificity. These methods also don’t reliably distinguish between EV subtypes.
Previously, investigators in the Yasui lab had developed zinc oxide nanowire devices capable of efficiently enriching EVs through charge interactions and hydrogen bonding. Further, the researchers noted that polyketone-coated zinc oxide nanowires improved the efficiency and purity of EV isolation within a microfluidic system designed for cancer diagnostics. Those findings led the team to explore whether polyketone chemistry could provide a more controlled method of attaching antibodies to the nanowires.
To do this, the team developed a platform based on N-hydroxysuccinimide ester-functionalized polyketones, known as pKNHS. They synthesized six pKNHS variants with different chain lengths and found that pKNHS 4.2 provided the most effective combination of nanowire stability and antibody immobilization.
The technology was first evaluated using cultured breast cancer cells. Antibody-free nanowires captured approximately 65% of CD9-positive EVs, while nanowires conjugated with CD9 antibodies captured efficiency of about 90%.
Next, the platform was testing using antibodies directed against ovarian cancer-associated markers CLDN3, FOLR1, and TROP2. These modified nanowires selectively recovered EVs from ovarian cancer cells and were subsequently used to isolate EVs from blood serum samples obtained from six patients with high-grade serous ovarian carcinoma and six individuals without cancer.
Analysis of the captured EVs showed distinct microRNA patterns of the EVs collected from cancer patients compared with those from the people without cancer. In total, the team identified 126 microRNAs shared among EVs captured using all three ovarian cancer markers. They also found unique microRNA populations linked to each marker, including 40 associated with CLDN3, 37 with FOLR1, and 45 with TROP2.
The system also facilitated the analysis of both EV membrane proteins and encapsulated microRNAs, which could scientists to better understand the relationships between surface markers and the associated molecular cargo.
Future work will focus on comparing the technology with existing clinical diagnostic methods and expanding its ability to capture additional EV subpopulations. The long-term goal is to apply the approach to noninvasive liquid biopsies and early diagnosis across a range of cancer types.
Last month, the Andes virus outbreak on a Dutch cruise ship departing from Argentina brought a transmission context for hantavirus, that was previously unprecedented, to the forefront. The Andes virus is the only member of the hantavirus family that is capable of efficient person-to-person spread through close contact with respiratory secretions. Other hantaviruses are typically spread through contact with infected rodents, making the Andes virus a much more significant public health threat.
While at sea, the outbreak spread among passengers and crew, infecting 13 people and killing three. The cruise passengers have since returned to their home countries, 23 in total. Because a person can carry the virus for weeks before showing any symptoms, health agencies are facing a complex challenge of identifying everyone who was exposed. There are currently no vaccines or preventive treatments approved for the virus; this travel-related outbreak brought the need for vaccine development to the forefront.
Researchers at The University of Texas Medical Branch (UTMB) had previously developed and tested two mRNA vaccines against intramuscular Andes virus challenge in golden Syrian hamsters (“1-methylpseudouridine-modified or non-modified mRNA modalities encoding the envelope glycoproteins, Gn and Gc, in a single open reading frame.”)
When tested in the Syrian hamster model, both mRNA vaccines were efficacious in hamsters using a two-dose regimen. Recognizing that a fast-moving international outbreak doesn’t allow time for patients to wait weeks between shots, the team retested the vaccines to determine whether a single dose would be effective.
Now, a new report shares the finding that the vaccine provided full protection against the Andes hantavirus after a single dose.
Alexander Bukreyev, PhD, head of the Laboratory of Viral Pathogenesis and Vaccine Development at UTMB, said that the group is working to fast-track these single-dose vaccines into human clinical trials.
The results exceeded expectations. When testing the vaccines in an animal model that mimics human disease, the scientists found that a single shot provided 100% protection against a lethal dose of the virus. Even when the researchers significantly lowered the dosage to a fraction of the original amount, the results remained definitive.
“Every vaccinated animal remained completely healthy and showed no symptoms or weight loss,” said Michelle Meyer, PhD, senior scientist in the Bukreyev Laboratory. “When we looked at the tissues from the vaccinated animals a month after infection, the virus was entirely gone. The vaccines triggered a powerful immune response, creating protective antibodies in as little as 14 days.”
Because the Andes virus can take a relatively long time to make a human severely ill, these fast-acting vaccines could serve a dual purpose, possibly functioning as an emergency tool for people who have already been exposed.
“If given quickly to high-risk contacts during an outbreak, such as the Andes virus situation on the cruise ship, the vaccines could theoretically jump-start their immune systems fast enough to intercept the virus—stopping it from replicating and preventing them from getting sick or spreading it further,” Bukreyev said.
Biotechnology company SonoThera has raised $125 million in an oversubscribed Series B financing round. The financing was led by Vida Ventures, with participation from ARK Invest, CureDuchenne Ventures, Leaps by Bayer, Otsuka Pharmaceutical, SymBiosis, UCB Ventures SA, Vivo Capital, and existing investors ARCH Venture Partners, Alexandria Venture Investments, Duquesne Family Office, Illumina Ventures, Johnson & Johnson Innovation – JJDC, Medical Excellence Capital, RA Capital, and Vertex Ventures HC.
SonoThera will use the funds to advance its lead programs in Duchenne muscular dystrophy (DMD) and autosomal dominant polycystic kidney disease (ADPKD) in the clinic. The funds will also support efforts to expand its pipeline of targeted redosable genetic medicines across multiple organ systems and scale its proprietary platform technologies for safe, targeted therapy delivery.
The company’s platform combines a proprietary ultrasound-mediated delivery technology dubbed RIPPLE, with a payload engineering platform dubbed PORE. The platforms are designed to support the development of DNA and RNA therapeutics, gene editing, and gene silencing approaches. SonoThera is using its tech to develop genetic medicines that it claims will address key limitations of conventional gene therapies including delivery challenges, payload size constraints, immune responses, safety events, and difficulties with redosing.
As Kenneth Greenberd, PhD, SonoThera’s co-founder and CEO, stated “we founded SonoThera to take a fundamentally different approach, with a platform designed to broaden the therapeutic possibilities of the field. We believe our technology has the potential to expand the range of diseases addressable by genetic medicines while enabling more precise, durable, safer, and repeatable therapies for patients.”
SonoThera has already demonstrated the targeted delivery and expression capabilities of its platform across multiple tissues, including skeletal muscle, heart, liver, kidney, adipose, and brain. It has also shown that it can deliver large payloads such as full-length dystrophin for DMD and RNA-based payloads for gene silencing applications in preclinical studies.
The company expects to initiate its first clinical trial in DMD in 2027.
Commenting on the financing, Rajul Jain, MD, managing director at Vida Ventures, said “we believe SonoThera, with its RIPPLE delivery and PORE payload engineering technologies, has the potential to unlock opportunities in diseases with significant unmet need that have been previously inaccessible to other genetic medicine approaches.”
In connection with the financing, Jain and Rakhshita Dhar, MS, vice president & head of Healthcare Venture Investments at Leaps by Bayer, have joined SonoThera’s Board of Directors.
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To the untrained eye, the chip is a piece of clear silicone about the size of a AA battery. Crisscrossing chambers within house hot pink and electric blue liquids that neatly cascade toward the device’s beveled edges.
Yet inside, invisible without a microscope, is the replicated microenvironment of a human liver. The pink and blue rivulets, each a millimeter wide, are endothelial and epithelial channels, respectively. Between them dance immune, stellate, and endothelial cells, complete with extracellular matrices and a membrane, hepatocytes galore. Together, they comprise the quad-culture model of Emulate’s Liver-Chip S1.
Lorna Ewart, PhD CSO, Emulate
“When you first look at it, you’re like, ‘That does this?’” said Lorna Ewart, PhD, CSO at Emulate, a Boston-based biotechnology firm specializing in organs-on-a-chip. “The engineering behind it is fairly complex.”
The chip, a marvel of photolithography, is assembled in layers of polydimethylsiloxane. A porous membrane separates the blue upper channel, which has a height of 1 mm, from the pink lower channel, which stands a mere 0.2 mm tall. Emulate prepares the multicellular framework for purchase and from there, researchers are free to experiment on the tissue-tissue interface in three dimensions.
“It’s a very elegant solution,” Ewart said. “When you place the cells in this device, you are starting to create an environment that feels like home for those cells.”
In the world of drug development, the advantages of organs-on-a-chip over traditional Petri dish cultures go beyond their 3D design, Ewart stressed. Microfluidics are at play, with perfusion the “secret sauce” that mimics human physiology.
“All of your tissues in your body are perfused,” Ewart said. “Recreating that in vivo-like environment is what makes these cells function as if they’re in the body, and therefore gives greater or more predictive data to the user.”
Emulate, whose founders began their work at Harvard University’s Hansjörg Wyss Institute for Biologically Inspired Engineering, is a key player in the explosion of the organ-on-a-chip industry. Valued at $227 million last year, the global market size is projected to soar to $3.4 billion by 2034, according to market research firm Straits Research.
This growth, Ewart said, comes down to one driver: Animal models are poor predictors of drug safety and efficacy
in humans.
Ancient problem meets futuristic solution
The vast majority of drug candidates—90%—fail in clinical trials, according to a 2022 report in the journal Acta Pharmaceutica Sinica B. That doesn’t include those that don’t make it past preclinical testing. The few drugs that are successful typically take more than 10 to 15 years each, and upward of $1 billion to $2 billion to go from discovery to market.
One reason for drugs’ limited success in this costly, lengthy pursuit is the inability of animal models to adequately simulate drug responses in humans.
Since antiquity, humans have relied on animals to help them understand their own anatomy and physiology. Though French chemist Louis Pasteur famously tested the rabies vaccine on animals before successfully doing so in humans in the 1880s, it wasn’t until the passage of the Food, Drug, and Cosmetic Act in 1938 that animal testing became the gold standard in U.S. clinical drug trials.
More than 80 years later, in 2022, the bipartisan Food and Drug Administration (FDA) Modernization Act 2.0 made animal testing optional. The new law encourages drug developers to conduct testing “in vitro, in silico, or in chemico, or a nonhuman in vivo test.” Organs-on-a-chip, which the FDA considers a type of microphysiological system, were listed as one such technology.
The FDA has continued to move away from animal testing. In March 2026, the agency issued draft guidance highlighting new approach methodologies (NAMs)—including organs-on-a-chip—that may be used instead.
“This draft guidance advances our commitment to replace animal testing with human-relevant, scientifically rigorous methods,” Secretary of Health and Human Services Robert F. Kennedy Jr. said in a recent statement. “Clear validation expectations will help modern tools earn regulatory confidence and speed safer, more effective therapies to patients.”
It’s a global effort. The U.K.’s Medicines and Healthcare products Regulatory Agency announced a commitment to “replace, reduce, or refine animal use in medicinal product development.” In Japan, the Pharmaceuticals and Medical Devices Agency established a NAMs Working Group. The Indian government recognizes NAMs as a valid preclinical endeavor.
Donald Ingber, MD, PhD, the scientific founder at Emulate and founding director of the Wyss Institute, has been a step ahead for the better part of two decades. In 2010, he and Dan Dongeun Huh, PhD, now a professor of bioengineering at the University of Pennsylvania and the co-founder and CSO of biotech firm Vivodyne, developed a “breathing” lung-on-a-chip. Their research, published in Science that year, is considered a seminal work in the organ-on-a-chip space.
In a video accompanying a 2010 Harvard Medical School news release about the research, Ingber described the chip as a “little, flexible device” designed “hopefully, someday, to replace animal studies.” Someday has arrived.
The FDA launched the pilot program, Innovative Science and Technology Approaches for New Drugs (ISTAND) in 2020 and adopted it as a permanent initiative in 2025. Part of Ewart’s job is to steer Emulate through this regulatory pathway. In doing so, she confronts one of the biggest hurdles in organ-on-a-chip expansion: standardization.
“When a tool is qualified, it can be used in a regulatory document without the FDA needing to reconsider or reconfirm its suitability,” Ewart said. “It saves the sponsor a lot of time, and it’s an acknowledgement that these tools perform very well. … The data that comes from them, they will use in their risk assessment of a drug as it moves into the clinic.”
Emulate was the first organ-on-a-chip company granted acceptance to ISTAND, Ewart said. The FDA noted its Liver-Chip S1 is designed to predict drug-induced liver injury, a major reason why drugs fail safety testing in trials and are withdrawn from the market.
“We’re in the final phase now of the program,” Ewart said. “Looking forward to trying to obtain qualification in 2027.”
Faster results for patients in need
As they continue their metamorphosis from futuristic concept to laboratory standard, organs-on-a-chip offer researchers and patients an unprecedented bench-to-bedside timeline.
Weiqiang Chen, PhD Professor NYU Tandon School of Engineering
While drugmakers and the general public alike stand to benefit from accelerated drug discovery, Weiqiang Chen, PhD, designs chips for patients who lack the luxury of time. Chen, a professor of biomedical, mechanical, and aerospace engineering at NYU’s Tandon School of Engineering in Brooklyn, helped develop the first immunocompetent leukemia-on-a-chip.
“It’s quite a different type of cancer,” Chen said. Most cancers form solid tumors, but leukemia, a liquid cancer, develops in the bone marrow. “It’s more challenging to generate the microenvironment for leukemia. … It involves a lot of immune cells, immune functions, and immune interactions.”
The leukemia-on-a-chip, commissioned by NYU Langone Health, is circular, roughly the size of a quarter. Green and vermilion pools surround a blue ring at the center. Within that lies a red liquid dot.
“Outside, we have one layer of osteoblasts, the bone cells, and inside are the central sinus and the vasculature and some mesenchymal stem cells,” Chen said. “All the immune cells are located within the vascularized niche, similar to real bone marrow.”
The technology allows Chen and his team at NYU’s Applied Micro-Bioengineering Laboratory to interrogate single cells. They can also observe how the cancer responds to chimeric antigen receptor T-cell therapy in real time—within a patient’s unique immune system.
The chips are constructed using a leukemia patient’s own cells. Meaning, Chen said, the observed therapeutic response is not only more accurate than it would be in an animal model but also patient-specific.
“We can help to identify responders, non-responders, or we can help screen out more efficient combination therapy for the specific patient for precision medicine purposes,” Chen said.
He acknowledged that the process is imperfect, yet strong enough to swiftly guide treatment. The chips take just half a day to build and yield results within weeks.
“We can fill the gap, providing a high throughput and also accelerated screening in three weeks,” Chen said. “We can screen many drugs at the same time.”
Chen pointed out that some patients have a weeks-long window in between chemotherapy and immunotherapy—a time crunch the leukemia-on-a-chip can accommodate.
The lab is also exploring other immunologic uses for organs-on-a-chip, including a lymph node-on-a-chip that can help validate new vaccines. In addition, in March, the NYU Grossman School of Medicine and Sage Bionetworks received a $25-million grant to launch the data hub and coordinating center for the National Institutes of Health’s (NIH) Complement-Animal Research in Experimentation program.
Though Chen will leave NYU in June to become the dean of the new School of Biomedical Engineering at Nanjing University in China, the work continues.
“It’s exciting for us to expand our research in the future to make a real impact,” Chen said.
Bone-deep discoveries, millimeters thin
Nearly 3,000 miles to the west, Avathamsa Athirasala, PhD, an assistant staff scientist at the Oregon Health and Science University (OHSU) in Portland, is studying other aspects of the bone in miniature.
“The bone is different from other tissues in how it feels and what it’s made up of,” she said. “It’s highly mineralized, it’s mechanically stiff, and it’s constantly being remodeled. It has a lot more forces being put on it.”
Avathamsa Athirasala, PhD Assistant Staff Scientist Oregon Health and Science University
Athirasala works in the Precision Biofabrication Hub, part of the OHSU Knight Cancer Institute, under founding director Luiz Bertassoni, DDS, PhD. Through their bone-on-a-chip, hub researchers are studying cancer metastasis.
For example, more than 80% of people with advanced prostate cancer experience bone tumors. A $2.5-million NIH grant awarded in April will help Athirasala’s team discover how.
“Some of these tumor cells—why are they attracted to bone? And why do they thrive in bone?” she asked. “Because they have never experienced an environment like bone.”
She added, “Using this model, we are able to try and maybe even understand how cancer progresses, or how it changes as it goes to a new environment.”
Athirasala is also investigating potential uses for the bone-on-a-chip in regenerative therapies. Soldiers, for instance, may have debilitating bone injuries that heal differently from fractures. A scaffold designed to regenerate bone may be a better treatment than a metal implant, and the chip could help evaluate patient reaction.
“What are the first things that the body starts doing in response to a foreign object? There will be inflammatory signals, there will be host stem cells that want to infiltrate in there and start remodeling it,” Athirasala said. “You can actually recreate the temporal aspects of this—what comes first, what comes later—in a chip.”
Problem and promise of precision
Athirasala delights in seeing solutions to biological problems play out before her. Within organs-on-a-chip, cells hold answers. Still, the devices’ possibilities aren’t endless—yet.
Precision medicine applications, in particular, face logistical roadblocks, she said.
“You have to get all the pipelines in place to be able to get patient cells, preserve them long enough, and get them to where the engineers are making these chips and incorporate them in the devices,” Athirasala said.
Preclinical drug testing that replaces animals with organs-on-a-chip is projected to curtail costs in the long run. Emulate, for example, expects its Liver-Chip alone to increase annual research and development productivity in the small-molecule drug development industry by $3 billion. But as with any new technology, for now, the chips themselves and the infrastructure required to sustain them aren’t cheap.
Market intelligence platform IndexBox estimates that in the U.S., single-chip readers cost about $10,000 each, while comprehensive systems that manage microfluidics run as high as $200,000. Chips are priced between $50 and $2,000, with assay kits and reagents hovering around $100 to $500.
Ewart, of Emulate, said the company doesn’t typically publish costs, which vary depending on customer needs.
What’s more, with each institution that builds its own organ-on-a-chip, standardization becomes harder to attain.
“Each one may have their own advantages, but no one can convince each other which one’s better,” said Chen, of NYU. “Without standards, we cannot really push this technology into practical use.”
Andrei Georgescu, PhD CEO and Co-founder Vivodyne
In the absence of device uniformity, Vivodyne, the Penn Engineering spinoff with offices in Philadelphia and outside San Francisco, is tackling the issue of reproducibility. CEO and co-founder Andrei Georgescu, PhD, saw a solution in end-to-end automation.
“If it is possible to scale up the production of these lab-grown tissues, then we have ourselves a substrate for solving what is the most challenging problem now in medicine,” he said, “which is, we don’t know how human biology responds very well to the perturbations that we make on it.”
The result not only eliminates human variation in lab technique but also allows Vivodyne to test more than 10,000 lab-grown tissues at once.
“We shrink what is like a state-of-the-art biotech lab into the footprint of a large desk,” Georgescu said. “Within each of these systems, we have complex confocal microscopy and a fridge and freezer and a robot arm with multiple tools for liquid handling, dispensing, and dosing these tissues, and we grow them within this platform.”
Vivodyne pairs its automated labs with artificial intelligence to create a feedback loop in experimental design, Georgescu said. The idea is to quickly identify druggable targets and pinpoint which drug candidates are most likely to succeed.
While complete bodies-on-a-chip remain a pipe dream, Vivodyne is among the companies investigating how different organs-on-a-chip interact with one another. Orlando-based Hesperos, for one, manufactures a Human-on-a-Chip® that can replicate several organs on a single device. TissUse, of Berlin, is developing multi-organ chips to mirror male and female environments: the HUMIMIC ChipXY and HUMIMIC ChipXX.
The burgeoning field of organ-on-a-chip drug testing lies at the intersection of bioengineering, pharmaceutical regulation, and data science. To Georgescu, at its heart, it’s also reassuringly straightforward.
“Just because biology is complex,” he said, “does not mean it is not already as simple as can be.”
Lindsey Leake is an award-winning, independent health reporter based outside Washington, D.C. She spent 15 years as a staff journalist at outlets including Fortune, the USA TODAY Network and Sinclair Broadcast Group. She holds an MA in Science Writing from Johns Hopkins University, an MA in Journalism and Digital Storytelling from American University, and a BA from Princeton University.
, with a payload engineering platform dubbed PORE
