Researchers in the laboratory of Professor Kripa Varanasi at MIT, working with collaborators at MIT and Johns Hopkins University, have developed a handheld device capable of gently collecting living cells from precise locations within tissue samples. Described in the journal Device, the system is designed to sample the fallopian tubes, where roughly two decades of research have revealed that many cases of high-grade serous ovarian cancer, the most common form of the disease, actually begin. Because precursor lesions in the fallopian tubes can be microscopic and extraordinarily difficult to sample, they have remained largely invisible to conventional diagnostic workflows.

The technical concept behind the device is elegantly simple, even if its execution required careful engineering. A 3D-printed microfluidic chip is pressed against the surface of freshly excised tissue, where one syringe creates a vacuum that seals the device against the specimen, ensuring that nothing leaks during operation. A second syringe then pushes fluid through a small microfluidic channel, producing a flow that applies shear stress parallel to the tissue surface. Rather than cutting or scraping cells away with a scalpel or brush, the flowing liquid gently detaches living cells from tiny, targeted sections of tissue, leaving the surrounding structure intact for conventional pathological examination.

“We came up with this device where one syringe creates a vacuum that holds it against the tissue, and a second syringe pushes liquid through it,” says Bert Vandereydt, an MIT postdoc and co-first author of the study. “The vacuum creates a seal, so nothing leaks, and then we locally apply what is basically a microfluidic chip on the tissue that gently shears the cells off.” The insight emerged from the lab’s deep experience with fluid-surface interfaces, and from conversations with surgeons at Johns Hopkins who observed that certain cells were loose enough to come off during routine washing and other procedures in the operating room.

The significance of collecting cells alive, rather than fixed in preservative, cannot be overstated. The traditional approach to examining removed fallopian tubes involves placing the tissue in a chemical preservative that maintains structure but kills the cells, making it impossible to grow them in culture. A pathologist must then painstakingly search thin sections under a microscope for cancerous or precancerous regions, a process that Varanasi describes as time-consuming and destructive to the cells. With the new technique, researchers can not only see what cells look like but recover them viable, cultivate them, grow them into organoids, and build living models of disease that show how cells from a specific patient behave.

In their study, the researchers demonstrated that the shear stress applied by the device can be tuned to different levels, and they compared their approach against other cell-collection workflows. The cells harvested with the fluidic method remained viable and grew in culture far more readily than those detached by conventional means. The tunability extends across disease types as well. Loose prostate cancer cells detach under stress as low as one pascal, whereas bone cancer cells proved far more tenaciously adherent, with only a few cells releasing even under five pascals of applied stress. As Vandereydt puts it, the approach is agnostic to the disease, which suggests broad utility well beyond ovarian cancer.

Proving the technology in real clinical conditions required an unusual level of dedication. The team tested the device on fresh human fallopian tube samples shipped from collaborators at Johns Hopkins, which meant staying on call for deliveries that could arrive at unpredictable times. “Sometimes, we’d get an email from our collaborators at 11 p.m. saying ‘There are two fallopian tubes coming tomorrow,'” Vandereydt recalls. After each experiment, the samples were returned for conventional pathology, ensuring that nothing was lost from the diagnostic record. From those fresh specimens, the team successfully collected living cells and converted them into organoids, the crucial building blocks for testing, disease modeling, and eventually personalized treatment development.

The project traces its origins to a fortunate convergence of clinical and engineering expertise. Rebecca Stone, a gynecologic oncologist at the Johns Hopkins University School of Medicine, has long advocated for risk-reducing fallopian tube removal for certain women at elevated risk, a procedure that can be performed after childbearing years while largely preserving normal hormone production. When Angela Belcher, MIT’s James Mason Crafts Professor, introduced Stone to Varanasi, the collaboration was born, funded by Break Through Cancer, a foundation that assembles interdisciplinary teams to attack the most stubborn problems in oncology. “This is exactly the kind of problem that benefits from bringing clinicians and engineers together,” Stone says. “We understand the clinical need, while the MIT team brings a very different perspective from fluid mechanics and engineering.”

The road ahead involves two distinct phases. In the near term, the researchers plan to apply the device to tissue that has already been removed from the body, a pathway that offers easier regulatory approval and could transform routine histopathology by allowing living cells to be harvested while the specimen is preserved for standard examination. Stone notes that integrating the technology into existing pathology workflows could create a powerful new way to study carcinogenesis and fundamental biology directly from human tissue. In parallel, Belcher’s group is developing optical approaches to identify suspicious regions of tissue, and the cell-collection device could then extract living cells from exactly those flagged locations. The longer-term ambition is bolder still: adapting the device to swab samples inside patients directly, enabling easier testing and earlier detection without surgery.

What makes this work resonate far beyond a single laboratory is the vision it points toward for cancer medicine as a whole. If clinicians can harvest living cells from specific, suspicious regions without destroying them, then diagnostics could evolve from static snapshots of preserved tissue into dynamic studies of living disease. Organoids grown from a patient’s own cells could be exposed to different therapies in the laboratory, revealing which treatments work before a patient receives a single dose, a genuine step toward personalized medicine. Varanasi credits Break Through Cancer with making the collaboration possible, noting that teams working on pancreatic cancer, brain cancer, leukemia, and other diseases all expressed how valuable better methods for obtaining living cells from specific tissue regions would be. For the researchers, the ultimate measure of success is human: “If this work can ultimately help women by enabling earlier detection of ovarian cancer, I would find that incredibly fulfilling,” Varanasi says. “That is really what motivates us — taking the science and engineering we develop in the lab and using it to make a difference in people’s lives.”

Subject of Research: A handheld microfluidic shear-stress device for collecting viable cells from fallopian tube tissue to improve early cancer detection

Article Title: New cell-collection device could improve early cancer detection

Article References: New cell-collection device could improve early cancer detection. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: ovarian cancer, microfluidics, fallopian tubes, early detection, organoids, living cells, personalized medicine, MIT, shear stress, cancer diagnostics, pathology, biomedical engineering

A new computational study published in the Annals of Biomedical Engineering by Yuval Gabso, Moshe Rosenfeld, and Idit Avrahami, researchers at Tel Aviv University and Ariel University in Israel, has now exposed a counterintuitive design paradox at the heart of these devices. The team used high-resolution computational fluid dynamics to compare four different micro-axial p-LVAD architectures across twenty distinct operating conditions, and their findings challenge a long-standing assumption in pump design. The results suggest that making a pump more hydraulically efficient can, under certain architectures, actually make it more dangerous to the blood it moves. The work was conducted at the Ariel Biomechanics Center and funded by the Israeli Ministry of Science and Technology.

The central question the researchers tackled is one of the most stubborn in biomedical engineering: how do you predict, reliably and early in the design process, how much mechanical damage a pump will inflict on blood? The classical approach relies on so-called Eulerian indices, which evaluate the flow field at fixed points in space and estimate blood damage from local stress levels, often using turbulence-based models. These methods are computationally fast and attractive for screening many design candidates. The alternative is Lagrangian particle tracking, in which thousands of virtual blood cells are released into the simulated flow and followed along their entire trajectories, accumulating stress exposure minute by minute as they travel through the pump. Lagrangian methods are far more faithful to the physics of blood trauma, because real cells do experience their damage cumulatively along a path, but they demand much more computational effort.

Whether the cheaper Eulerian approach can be trusted in the tight, fast, complex geometry of a micro-axial pump has been an open question, and it is precisely the gap this study set out to close. The team evaluated two Eulerian turbulence-based hemolysis indices, labeled HI1 and HI2, against two Lagrangian metrics: the median stress accumulation experienced by tracked particles, and the mean supra-threshold exposure time, which measures how long cells spend above damaging stress levels. Four pump configurations were modeled, three of them using a discharge-type architecture and one using a suction-type configuration featuring an expanding hub, a design element intended to smooth the flow and prevent separation from the impeller surfaces.

The paradox emerged from the suction-type design. The expanding hub did exactly what it was engineered to do: it improved hydraulic efficiency by preventing flow separation, meaning the pump could deliver the required pressure and flow with less wasted energy. But the same geometric feature created a high-velocity bottleneck inside the pump, a narrow passage through which blood had to accelerate dramatically. That acceleration drove up the bulk shear stress throughout the device, and shear stress is the primary mechanism by which mechanical pumps destroy red blood cells. In other words, the more efficient the suction-type pump became, the more it stressed the blood passing through it. Efficiency and hemocompatibility, two goals designers usually pursue together, turned out to pull in opposite directions in this architecture.

Just as striking was the failure of the Eulerian indices to detect any of this. When the researchers examined how the two turbulence-based indices behaved across the twenty operating conditions, they found that both functioned essentially as RPM trackers. Their values correlated almost perfectly with the Womersley number, a dimensionless parameter related to the pulsatile operating conditions, with correlation coefficients exceeding 0.94. But that near-perfect correlation was a symptom of a deeper problem: the indices were responding almost entirely to how fast the pump was spinning, not to the intricate geometry inside it. They completely missed the geometry-induced stress peaks created by the expanding hub, the very feature that distinguished the suction design from its discharge-type siblings and drove the paradoxical blood damage.

The Lagrangian metrics told a fundamentally different and richer story. By following virtual cells along their actual paths, the median stress accumulation and mean supra-threshold exposure time captured the multivariate reality of mechanical loading inside the pump, sensitive to both operating conditions and architectural details. A cell that lingers in a high-shear bottleneck accumulates far more damage than one that flashes through a brief stress zone, and only a trajectory-based method can register that distinction. The authors conclude that for micro-axial pumps, where bulk shear stress is the dominant damage mechanism, Eulerian turbulence models are simply insufficient, and that Lagrangian particle tracking must remain the high-fidelity standard for evaluating and optimizing these devices.

Beyond its methodological verdict, the study carries a practical design message. The three discharge-type architectures consistently offered a more favorable fluid dynamic profile, mitigating the high-shear stress exposure that plagued the suction configuration. For engineers developing the next generation of percutaneous heart pumps, this suggests a compelling strategy: favor architectures in which the flow is decelerated and discharged in a controlled manner rather than squeezed through accelerating bottlenecks, even if the raw hydraulic efficiency numbers look less impressive on a datasheet. The finding resonates with clinical observations that hemolysis, the destruction of red blood cells, remains a recognized complication of micro-axial support, and with prior work from the same group showing that impeller hub design significantly influences both pump performance and predicted blood damage.

The stakes extend beyond red blood cells. Mechanical stress inside these pumps also unfolds von Willebrand factor, a large protein essential for normal clotting, and activates platelets, the cellular fragments that initiate thrombosis. Shear-mediated platelet activation is a well-documented pathway to device-induced thrombosis, while the loss of functional clotting proteins paradoxically increases bleeding risk, so a single design flaw can simultaneously promote clots and hemorrhage. Understanding exactly where and how long cells are stressed inside a pump is therefore not an academic exercise; it directly shapes the safety profile that patients experience in the intensive care unit, where these devices are often deployed as a bridge during the most critical hours of cardiac illness.

The study also arrives at a moment when the use of percutaneous ventricular assist devices is expanding rapidly, with growing clinical evidence and debate about their outcomes in cardiogenic shock and high-risk interventions. As devices shrink and operating speeds climb, the margin for fluid dynamic error narrows, and the tools used to vet new designs matter more than ever. By demonstrating that fast, turbulence-based screening indices can be blind to the very geometric features that determine blood damage, the Israeli team has issued a caution to the field: computational shortcuts that work for large pumps may quietly mislead designers of micro-axial machines. The paradox they documented, in which a smarter-looking geometry trades efficiency for blood trauma, is a vivid reminder that in the miniature world of catheter-mounted heart pumps, the fluid that keeps us alive is also the most delicate component in the machine.

Subject of Research: Computational fluid dynamics analysis of blood damage in percutaneous micro-axial left ventricular assist device designs

Article Title: The Efficiency-Hemocompatibility Paradox: A Comparative Lagrangian and Eulerian Analysis of Micro-axial p-LVAD Architectures

Article References: Gabso, Y., Rosenfeld, M., & Avrahami, I. (2026). The Efficiency-Hemocompatibility Paradox: A Comparative Lagrangian and Eulerian Analysis of Micro-axial p-LVAD Architectures. Annals of Biomedical Engineering. https://doi.org/10.1007/s10439-026-04406-0

Image Credits: AI Generated

DOI: 10.1007/s10439-026-04406-0

Keywords: p-LVAD, micro-axial pump, hemocompatibility, hemolysis, computational fluid dynamics, Lagrangian particle tracking, Eulerian indices, shear stress, platelet activation, cardiogenic shock, mechanical circulatory support, pump design

Amyloid fibrils are ordered protein assemblies that accumulate in tissues in a family of devastating disorders, including Alzheimer’s disease and Parkinson’s disease. In amyloidogenic light chain disease, often abbreviated as AL amyloidosis, the fibrils are built from antibody light chain proteins and gather most prominently in the heart. There, the deposits stiffen the cardiac muscle and progressively impair its ability to pump blood. What has puzzled scientists is precisely why the heart becomes such a favored site of deposition. The new study points to an answer rooted in physics rather than chemistry alone: the very mechanics of blood flow through the beating heart’s vessels may actively drive the proteins out of their soluble state and into fibrils.

The shear stress exerted on proteins within cardiac blood vessels has long been suspected of promoting amyloid formation, but the underlying mechanism remained unclear. Lead author Yuji Goto and his colleagues faced a fundamental experimental obstacle: it is extremely difficult to design an artificial system that faithfully mimics the constant changes in volume and mechanical stress that the beating heart imposes on the blood and everything dissolved in it. Blood vessels narrow and widen with each pulse, flow speeds fluctuate, and proteins suspended in the plasma experience shifting patterns of friction and pressure. Capturing that dynamic environment in a laboratory dish, where solutions typically sit still in uniform conditions, has been a persistent challenge in the field.

The Osaka team’s solution was elegantly mechanical. They employed a peristaltic pump, a device that moves fluid by alternately compressing and releasing a flexible tube, pushing the liquid along in waves much as the digestive tract moves food. This arrangement reproduces the pulsatile, pressure-varying character of blood flow in a way that static cuvettes cannot. To watch what happened to the proteins inside, the researchers used thioflavin T fluorescence microscopy, a standard and sensitive technique in which a dye binds specifically to aggregated protein structures and lights up when it does. Any emerging amyloid fibrils therefore announce themselves as bright fluorescent signals, allowing the team to track amyloid formation in real time and, crucially, to see exactly where within the tubing it began.

The results were, in the researchers’ own assessment, very intriguing. The fibrils did not appear randomly along the length of the tube. Instead, they started to form preferentially in the narrow vertices of the semicircular tubing, the points where the geometry was most tightly constricted. Senior author Hirotsugu Ogi noted that this spatial constraint appeared to enhance amyloid formation in the presence of shear stress. In other words, neither crowding nor flow alone tells the whole story; it is the combination of molecules being physically squeezed into a small space while being subjected to mechanical shear that tips them over the threshold into aggregation. The analogy to rush-hour traffic holds: it is the junction of high density and constrained passage where problems begin.

To test this principle in a more controlled and addressable format, the team pumped the protein solution through a microchannel grid, a microscopic labyrinth of perpendicular channels etched into a substrate. Once again, amyloids tended to form at the intersections of the crossing channels, the spots where flow collided, geometry was tightest, and shear was presumably greatest. Remarkably, the researchers found they could partly clear these deposits simply by pressing down on a nearby channel, altering the pressure of the flow and washing the aggregates away. This demonstrated that the amyloid formation in their system was not an irreversible one-way process but remained sensitive to the mechanical conditions of the surrounding fluid.

Chemistry provided an even more complete reset. When the team added guanidine hydrochloride, a powerful denaturant that helps unfold and dissolve proteins, the remaining amyloids were completely cleared from the grid system. This confirmed that the fluorescent deposits were indeed protein aggregates that could be dissolved once the stabilizing structure of the fibrils was disrupted. The finding matters because it suggests that amyloid deposits formed under mechanical stress in the vasculature are not necessarily permanent fixtures; with the right intervention, they may be susceptible to removal, a possibility with obvious therapeutic appeal for diseases in which current treatments mainly aim to slow the production of the amyloidogenic protein rather than clear what has already accumulated.

The peristaltic pump setup also yielded a surprise involving a familiar dietary molecule. In a separate experiment, the team examined epigallocatechin gallate, a green tea compound previously studied for its anti-amyloid properties. They found that it could both prevent and reverse amyloid formation, but it did so in two distinct ways depending on the concentration used. One of these mechanisms had not been observed before, hinting that the compound’s interaction with aggregation-prone proteins is more complex and potentially more versatile than previously appreciated. While the study does not establish green tea as a treatment, it identifies a chemically well-defined molecule whose behavior under flow conditions could guide the design of future anti-amyloid agents.

Taken together, the findings show that amyloid formation and deposition in blood vessels occur due in part to both mechanical stress and blood vessel geometry, as Goto summarized. This reframes AL amyloidosis, and potentially other amyloid diseases with vascular involvement, as conditions shaped by biomechanics as much as by biochemistry. The coronary arterioles, with their small diameters and the relentless pulsing of the heartbeat, provide exactly the combination of constriction and shear that the Osaka experiments identify as the danger zone for aggregation-prone proteins. It is a compelling explanation for the cardiac tropism of light chain amyloid deposits, and one that emerges directly from observation rather than inference.

Methodologically, the study represents a significant advance in itself. By combining a peristaltic pump and microchannels with fluorescence microscopy, the research team achieved the difficult feat of observing the early stages of amyloid formation as they happened, in a geometry and flow regime relevant to the cardiovascular system. Looking forward, the work suggests that a combination of mechanical pressure and chemical inhibitors could help dissolve amyloids after they have formed, opening a possible avenue for intervention. More broadly, pinpointing the physical triggers of aggregation may help researchers better understand how amyloidosis develops in the body and support future efforts to assess disease risk in patients, potentially identifying who is most vulnerable before deposits begin to damage the heart.

Subject of Research: Mechanically induced amyloid formation by amyloidogenic light chain proteins under shear stress and spatial constriction

Article Title: Little space and a lot of flow spark amyloid formation

Article References: Little space and a lot of flow spark amyloid formation. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: amyloid fibrils, AL amyloidosis, shear stress, light chain protein, peristaltic pump, thioflavin T fluorescence, microchannels, epigallocatechin gallate, guanidine hydrochloride, cardiac amyloid deposition, protein aggregation, The University of Osaka

The research team, working at the University of Minnesota under protocols approved by the institution’s animal care committee, isolated primary hepatocytes from Sprague–Dawley rats using a two-step perfusion method. Livers were first flushed with University of Wisconsin solution, then perfused ex vivo with Krebs–Henseleit buffer followed by collagenase to digest the tissue architecture, after which gentle mechanical disruption released the cells. Trypan blue exclusion confirmed viabilities between 95 and 98 percent, ensuring that the starting material was healthy enough for the demanding aggregation process ahead. Each experimental condition drew on hepatocytes from a single isolation, a design choice that minimized inter-isolation variability and allowed the investigators to attribute differences in spheroid morphology specifically to the mechanical and seeding parameters under test.

The formation method itself is strikingly simple. Cells were plated at either 1.0 or 1.5 million cells per milliliter in 20 milliliters of spheroid formation media in rectangular Mayo dishes, which were then placed on rocker platforms housed inside a standard humidified carbon dioxide incubator at 37 degrees Celsius. The team tested five rocking speeds—7, 10, 12, 15, and 18 cycles per minute—over seven days of culture, and to rule out instrument-specific artifacts they ran matched conditions on two different commercial rocker platforms. After modest adjustment of speed, tilt angle, and inoculation density, the two platforms produced comparable spheroid size distributions, suggesting that the underlying physics of the system, rather than any particular device, governs the outcome. Within 24 hours, media was exchanged from spheroid-forming to spheroid culture conditions, and fluorescent live-dead staining with acridine orange and propidium iodide revealed smooth-bordered spherical aggregates with nearly complete viability.

The headline finding is a clean inverse relationship between rocking speed and spheroid size. At day 7, mean spheroid diameters measured 199 micrometers at 7 cycles per minute, 173 at 10, 129 at 12, 90.9 at 15, and just 80.2 micrometers at 18 cycles per minute. Median spheroid areas told the same story, falling from roughly 29,400 square micrometers at the slowest speed to 4,300 square micrometers at the fastest. Statistical analysis using the Kruskal–Wallis test confirmed significant effects of both culture day and a speed-by-day interaction on spheroid area, with post hoc Mann–Whitney comparisons showing the inverse speed-size relationship held at every time point from day 1 through day 7. The physical explanation is intuitive: faster rocking imposes greater shear forces and reduces the contact time available for cells to find and bind one another, while slower motion permits extended cell-cell interaction and larger aggregate growth.

There is, however, a floor to the relationship. At 7 cycles per minute, consistent spheroids did not appear until day 3, and in some dishes they never formed at all, presumably because the kinetic energy available for aggregation fell below a critical threshold. The team also observed a characteristic sinusoidal pattern in spheroid size across the week: aggregates grew for the first several days, peaked around days 3 to 5, and then contracted. At 10 cycles per minute, for example, mean area rose from about 13,750 square micrometers on day 1 to a peak of 26,730 on day 4 before settling back to roughly 22,500 by day 7. The authors attribute this shrinkage not to cell loss but to compaction, as maturing intercellular junctions and cytoskeletal remodeling draw the aggregate into a tighter, denser sphere.

Inoculation density provided the second, independent control axis. Holding speed constant at 15 cycles per minute, cultures seeded at 1.5 million cells per milliliter produced significantly larger spheroids than those seeded at 1.0 million at every time point measured, with day 7 mean areas of 7,203 versus 5,627 square micrometers. A significant density-by-day interaction indicated the magnitude of the effect shifted over the culture period, but the overall temporal pattern of early expansion followed by stabilization was preserved. The mechanism again follows from simple probability: more cells per milliliter means more frequent cell-cell encounters, greater aggregate stability, and ultimately larger and more numerous spheroids. Together, speed and density give labs a two-dimensional parameter space in which a desired spheroid size can be targeted rather than left to chance.

Critically, the team showed that size tuning is biologically meaningful, not merely a morphological curiosity. Urea production normalized to DNA content peaked at intermediate rocking speeds, with a median of about 3.47 micrograms per microgram at 12 cycles per minute, while the slowest condition at 7 cycles per minute produced almost none—consistent with diffusion-limited metabolism in oversized aggregates—and production declined again at the highest speeds, possibly reflecting shear stress or insufficient cell-cell signaling. Albumin and urea output both climbed steadily over ten days of culture, with albumin rising from a median of roughly 1,087 nanograms per microgram DNA on day 1 to about 1,534 by day 10. When converted to per-cell terms, these spheroids secreted an estimated 7 to 9 micrograms of albumin per million cells per day, several-fold higher than reported values for static two-dimensional hepatocyte cultures, and urea output by day 7 exceeded that of conventional hepatocyte monolayers.

Efficiency and variability metrics rounded out the practical picture. Volumetric analysis on day 4 estimated that a median of 86 percent of seeded hepatocyte volume had been incorporated into spheroids, with four of five datasets clustering between 73 and 95 percent, the lower values likely reflecting occasional cell adherence to dish walls and the tendency of compacting spheroids to be undersized by diameter-based volume estimates. Size dispersion, quantified by the coefficient of quartile variation, was widest on day 1—as expected during initial aggregation—and converged to a stable 21 to 24 percent by day 7 across all speeds, a range the authors note is acceptable for bioartificial liver applications even though static microwell methods can achieve tighter distributions on the order of plus or minus 10 to 20 micrometers.

The authors are candid about limitations. All experiments used primary rat hepatocytes, and interspecies differences in cytochrome P450 expression, metabolic capacity, and cell-cell dynamics mean extrapolation to human cells requires caution, though the underlying physical principles should generalize. Size was quantified from two-dimensional images assuming ellipsoidal geometry, and long-term culture beyond seven days was not assessed. Absolute parameter values may also need recalibration on different rocker platforms. Still, the study’s contribution is a framework rather than a recipe: by demonstrating that two universally available variables reproducibly govern spheroid dimensions while preserving metabolic function, the work hands bioartificial liver engineers, toxicologists, and regenerative medicine researchers a scalable, inexpensive tool for standardizing one of the field’s most important building blocks—no specialized equipment required.

Subject of Research: Tunable control of hepatic spheroid size through rocking speed and cell inoculation density

Article Title: The effect of rocking speed and cell inoculation density on hepatic spheroid size: A simple method for size modulation

Article References: Megaly, M. G., Tobolt, D., Chen, A. A.-F. D., Namsrai, B.-E., Fisher, B., Rao, J. S., Ramesh, S., Chimedtseren, A., Nyberg, S. L., Clemens, M., Lee, C. Y., Bischof, J. C., & Finger, E. B. (2026). The effect of rocking speed and cell inoculation density on hepatic spheroid size: A simple method for size modulation. Bioengineering & Translational Medicine, 11(5), Article e70154. https://doi.org/10.1002/btm2.70154

Image Credits: AI Generated

DOI: 10.1002/btm2.70154

Keywords: hepatic spheroids, bioartificial liver, hepatocytes, rocking speed, inoculation density, spheroid size, drug toxicity testing, regenerative medicine, 3D cell culture, urea production, albumin secretion, shear stress

Suzanne Gaston Eskin, known to everyone as Suzie, was born in Houston, Texas, in 1939 and earned her bachelor’s and master’s degrees in biology at Rice University before completing a doctorate in zoology at the University of Texas at Austin in 1969. Her early career at Baylor College of Medicine placed her alongside the legendary cardiac surgeon Dr. Michael DeBakey, where she contributed to the development of early generations of left ventricular bypass pumps. That work posed a deceptively simple question: why do artificial surfaces and vascular grafts fail inside the body? Her answer was to bring the living cells of the vessel wall into the laboratory, isolating and culturing endothelial and smooth muscle cells on synthetic substrates and measuring how they responded to the physical forces associated with blood flow. These in vitro vascular cell culture models became one of her most enduring gifts to the scientific community, allowing researchers everywhere to dissect tissue-level responses to injury and disease under controlled conditions.

Larry Vern McIntire arrived at Rice University in 1970 as a freshly minted chemical engineer, holding degrees from Cornell and Princeton and a deep expertise in fluid mechanics. Where biologists saw cells, Larry saw systems governed by shear stress, viscosity, and transport phenomena. He applied that training to cardiovascular physiology with a rigor that transformed the field, rising to chair the Department of Chemical Engineering in 1981, direct the Institute of Biosciences and Bioengineering in 1991, and found the Department of Bioengineering in 1997. In 2003 he took the helm of the joint Georgia Institute of Technology and Emory University Biomedical Engineering department, expanding it into a program of national and international prominence before his retirement in 2013. His election as a fellow of the National Academy of Engineering, along with four other professional societies, reflected a career spent building bridges between engineering and medicine.

The technical heart of their partnership lay in the flow chamber. Larry innovated parallel plate flow chambers into continuous-flow systems that could sustain living cell cultures for long periods under precisely controlled shear stresses, while complementary devices stretched cells to mimic the cyclic wall stresses of a beating artery. With these tools, the couple and their collaborators made a discovery that now sits in every mechanobiology textbook: endothelial cells respond differently to distinct mechanical forces, altering the secretion of molecules such as prostacyclin and tissue plasminogen activator depending on the flow regime they experience. This gave rise to the concept of mechanochemical signal transduction, the idea that mechanical stimuli are converted into biochemical instructions inside the cell. Later, using high-throughput gene expression methods, they identified mechanosensitive genes that no one had previously suspected of playing a role in vascular biology, opening research directions that continue today.

Their flow systems also illuminated some of medicine’s most stubborn clinical problems. In sickle cell disease, the couple showed that adhesion between sickled erythrocytes and endothelial cells is dramatically enhanced under shear conditions, marking a key initiating event in the microvascular occlusion that causes excruciating pain crises. Crucially, they established that vaso-occlusion is not simply a consequence of stiffened red blood cells clogging narrow vessels, but a dynamic, flow-dependent process driven by endothelial activation, including the release of ultra-large von Willebrand factor multimers and the expression and shedding of adhesion molecules. Vaso-occlusion, in other words, is a coupled biomechanical and biochemical process, a reframing that unified previously separate lines of research and suggested new therapeutic targets.

The same experimental logic extended to inflammation and cancer. Their studies demonstrated that selectin ligands coordinate the initial rolling and adhesion of neutrophils to inflamed endothelial cells under venous shear conditions, while β2 integrins mediate the subsequent transmigration into tissue, and that these same interactions govern the formation of neutrophil-platelet aggregates in flowing blood. These were among the first studies to identify specific molecular pathways for force-selective cell adhesion, and they spearheaded mechanobiologically unified models of sickle cell pathophysiology, inflammation, and tumor cell adhesion during metastasis. The message was consistent: to understand how cells behave in the bloodstream, one must understand the physics of the bloodstream.

Blood clots themselves proved equally obedient to mechanical principles. Drawing on his training in non-Newtonian fluid mechanics, Larry investigated the viscoelastic properties of clots long before modern high-resolution microscopy existed, arguing that clot strength depends not only on platelet density but also on platelet aggregability and clot contractility. By adapting real-time visualization techniques from their flow chambers, Larry, Suzie, and collaborators showed that different hemostatic mechanisms regulate distinct phases of mural thrombus formation, and that dynamic adhesion models are essential for evaluating antiplatelet therapies. Perhaps most elegantly, their work on platelet interactions with von Willebrand factor revealed catch-slip bonds, molecular attachments that strengthen under increasing force before eventually releasing. This counterintuitive behavior explains why platelets and von Willebrand factor dominate arterial thrombi but not venous ones, a distinction of direct relevance to heart attack and stroke. The couple’s curiosity even reached into the cytoskeleton, where atomic force microscopy and molecular dynamics simulation revealed catch-slip bonds in actin regulated by signaling molecules.

Beyond the laboratory, the couple built institutions and, just as deliberately, built people. Larry mentored nearly one hundred graduate students and postdoctoral fellows, co-advising thirty-one doctoral students with Suzie. Their laboratory attracted trainees from across the globe from the 1970s onward, and the tribute emphasizes that their commitment to international and women scientists was practical rather than symbolic: they placed trainees in positions to succeed and expected them to do so. Many of those trainees now hold leadership positions across academia and industry. Larry also championed tissue engineering in its infancy, co-editing the early reference volume Frontiers in Tissue Engineering in 1998, launching an annual summer short course now in its thirty-third year, and chairing a federal panel whose report guided international investment in the field. With colleagues he co-authored the textbook Bioengineering Fundamentals, and as Editor-in-Chief of the Annals of Biomedical Engineering from 2002 to 2009 he doubled the journal’s impact factor and helped spawn two sister journals, defining biomedical engineering as an independent and impactful discipline.

Suzie Eskin passed away on March 27, 2024, after bravely battling Lewy body disease, and Larry McIntire passed away on January 23, 2026, in Stone Mountain, Georgia. What they leave behind is more than a bibliography of more than 250 publications, from the effects of mechanical trauma on leukocytes to endothelial cell migration modeled with Markov chains. They leave a way of thinking, in which the pulsing, shearing, stretching forces of the circulatory system are treated as first-class biological signals, and in which engineering rigor and biological curiosity are inseparable. Their former students, now writing their memorial, pledge to carry forward the same curiosity, integrity, and kindness that defined two scientists who proved that the best collaborations, like the best bonds, can grow stronger under load.

Subject of Research: Memorial tribute to vascular mechanobiology pioneers Dr. Suzanne G. Eskin and Dr. Larry V. McIntire

Article Title: In memory of Dr. Suzanne G. Eskin (1939–2024) and Dr. Larry V. McIntire (1943–2026)

Article References: Brey, E. M., Conway, D. E., Diamond, S. L., Frangos, J. A., Gonzalez, A. L., Hubbell, J. A., Konstantopoulos, K., Lawrence, M. B., Lee, C.-Y., Nguyen, K. T., Ramasubramanian, A. K., Shiu, Y.-T., Williams, M. R., & Yee, A. (2026). In memory of Dr. Suzanne G. Eskin (1939–2024) and Dr. Larry V. McIntire (1943–2026). Annals of Biomedical Engineering. https://doi.org/10.1007/s10439-026-04387-0

Image Credits: AI Generated

DOI: 10.1007/s10439-026-04387-0

Keywords: mechanobiology, vascular biology, endothelial cells, shear stress, sickle cell disease, thrombosis, von Willebrand factor, tissue engineering, biomedical engineering, mentorship, catch-slip bonds, Rice University