Tag: Academic research

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.

“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.

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.”

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.”

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.

The post Organs-on-a-Chip Offer “Elegant Solution” to Quandary of Animal Models in Drug Design appeared first on Inside Precision Medicine.