Mechanical stiffness is a critical physical property of soft biological tissues that is closely associated with physiological and pathological states. However, the quantitative mechanical characterization of small and soft samples remains challenging due to the limited sensitivity and poor portability of conventional compression testing systems. Here, we present a compact, benchtop micro-load compression testing platform designed for the evaluation of small, soft biological tissues. The device enables reproducible measurements under millinewton-level loading and micrometer-scale displacement while maintaining a simple, portable configuration. Using collagen- and gelatin-based gel samples with spherical and cylindrical geometries as biomimetic models, we demonstrate the system's performance across different materials, temperatures, and sample geometries. To address the predominance of nonlinear deformation in soft materials, we introduce a model-free stiffness index, which is defined as the local slope of the semi-logarithmic nominal stress–strain relationship. This approach allows for a robust relative comparison of mechanical responses without assuming specific constitutive models or material homogeneity. The proposed platform combines practical operability with analytical robustness, providing a versatile tool for the rapid mechanical screening of soft tissues and biomimetic materials. Its compact design and compatibility with controlled environments make it ideal for applications that require the flexible, high-sensitivity mechanical assessment of limited, fragile biological samples.

Plasma discharges at gas–liquid interfaces are widely investigated for water treatment, medical applications, and materials processing because they generate reactive species directly in liquids. However, most previous studies have employed configurations in which solid electrodes were partially exposed to the gas phase, making it difficult to isolate the intrinsic role of the liquid in determining discharge behaviour. In this study, both metallic electrodes were fully immersed in the liquid, and plasma was generated in the gas region between the two opposing liquid surfaces, thereby eliminating solid–gas interfaces. By varying the conductivity and arrangement of phosphate-buffered saline (PBS) and ultrapure water (UPW), two distinct discharge regimes were identified under identical driving conditions. PBS–PBS produced a spark-to-DC-glow transition with pronounced interfacial heating and enhanced chemical production, whereas UPW-containing systems exhibited dielectric barrier dischargelike behaviour characterized by transient streamers, minimal gas heating, and reduced chemical yields. These findings demonstrate that the liquid phase acts as an active structural component, governing the discharge regime and plasma-induced chemistry while shaping the spatial distribution of optical emission. This work advances the fundamental understanding of liquid–gas–liquid plasma systems and provides a basis for selective control of discharge regimes through liquid-property design.

Low-temperature plasma is increasingly used to modulate chemical reactions at liquid interfaces, yet how plasma–solution interactions influence molecular assembly and crystallization remains poorly understood. Controlling crystal polymorphs is particularly challenging because metastable phases are often difficult to access reproducibly using conventional solution chemistry. Here, we show that direct exposure of aqueous mannitol solutions to dielectric barrier discharge plasma selectively promotes crystallization of the metastable δ polymorph. Plasma treatment yields δ-form contents approaching 90–95%, whereas charge-only conditions or plasma-treated solvent alone produce only the stable α/β forms, indicating that neither electrostatic charging nor solution chemistry alone explains the transition. Spectroscopic analyses reveal two coupled effects: plasma-generated reactive species induce partial dehydration and dehydrogenative condensation of mannitol, while direct plasma–solute contact introduces transient charge states that perturb intermolecular packing during nucleation. These findings identify plasma as a dual chemical-electrostatic driver that biases crystallization pathways toward otherwise inaccessible polymorphs, establishing a strategy for plasma-assisted crystal engineering.

Aqueous two-phase system (ATPS) droplets in cells act as fluidic microreactors by concentrating biomacromolecules. Inspired by this phenomenon, dextran-rich microdroplets formed in an ATPS with polyethylene glycol have been explored as artificial microreactors for sensitive detection and spatiotemporal control of biochemical reactions. However, the rapid fusion of the microdroplets into bulk phase separation has limited practical applications of this approach. Here, we report the stabilization of dextran-rich microdroplets using supramolecular nanofibers of an azobenzene-appending self-assembling peptide (AzSAP). Physicochemical characterization and structural analyses elucidate the mechanism of nanofiber formation and its role in droplet stabilization. The nanofiber network prevents droplet coalescence while maintaining macroscopic fluidity, thereby enabling highly sensitive quantitative virus detection via microfluidic analysis by confining infecting viruses within droplets. Furthermore, the photo-responsive properties of the AzSAP allow dynamic control over droplet size and intra-droplet virus activity, highlighting its exceptional potential as a platform for programmable artificial microreactors.

A stent maintains normal blood flow by expanding a stenotic artery from the inside. However, current stents are mechanically sub-optimized and can exert excessive forces on the vascular wall, leading to inflammation, late thrombosis, and in-stent restenosis. Optimizing the mechanical performance of stents requires not only reproducing the mechanical field within the stented vessel but also evaluating endothelialization, which serves as a key biological indicator of vascular neointimal formation. To this end, this study aimed to develop a three-dimensional in vitro stent endothelialization model that enables quantitative evaluation of endothelial responses under physiologically relevant mechanical conditions and to provide detailed fabrication protocols for its construction. Polydimethylsiloxane (PDMS) was used to mimic the adventitial structure of arteries. Human carotid artery endothelial cells (HCtAECs) were then seeded on the luminal surface and cultured for 24 h to form a confluent monolayer (intima). The constructed model was installed in the flow-exposure culturing system, and hemodynamic stimuli (two types of shear stress (SS); 0.5 Pa and 2.3 Pa) were applied to the HCtAECs inside to reproduce the physiological state of blood vessels. A self-expanding stent was then placed in the model during perfusion culture to evaluate in-stent endothelialization under controlled flow conditions. We examined the performance of the developed model based on quantitative evaluations of endothelial morphology in response to SS and in-stent endothelialization. Exposure to SS for 24 and 48 h caused endothelial orientation and elongation in the direction of flow, confirming the physiological responses of blood vessels. Furthermore, spatial and temporal analyses of in-stent endothelialization confirmed that the model can reproduce key biological processes associated with vascular neointimal formation in the presence of mechanical stimulation. The present model successfully integrates the mechanical and biological aspects of stent–vessel interaction, providing a reproducible platform for evaluating in-stent endothelialization under physiologically relevant conditions. This system can serve as a powerful tool not only for the quantitative assessment of endothelial dynamics but also for guiding the optimization of mechanical forces in stented blood vessels. Consequently, it offers a foundation for designing next-generation stents that promote rapid endothelialization and reduce the risk of restenosis and thrombosis.

Three-dimensional (3D) cell cultures, such as spheroids, are indispensable models for investigating cellular behaviors and responses under conditions that closely resemble in vivo environments. Conventional imaging techniques, including optical microscopy, are often limited by penetration depth, complicating the analysis of structural and biochemical changes within dense 3D systems. This study demonstrates the application of ultrasound imaging for the non-invasive evaluation of internal dynamics in cancer spheroids. Scattering-based acoustic parameters revealed spatial variations in amplitude and brightness density, correlating with cellular proliferation, apoptosis, and necrosis. Amplitude in central regions progressively decreased after Day 3, approaching near-zero by Day 15, reflecting necrotic core formation. Artificial inhibition of myosin contractility significantly influenced these patterns, providing insights into biomechanical contributions to spheroid organization. The findings establish ultrasound imaging as a label-free, high-penetration technique capable of addressing critical challenges in 3D culture analysis, offering new opportunities for studying cellular dynamics in spheroids and organoid models.

Blood glucose levels fluctuate during daily life, and the oxygen concentration is low compared to the atmosphere. Vascular endothelial cells (ECs) maintain vascular homeostasis by sensing changes in glucose and oxygen concentrations, resulting in collective migration. However, the behaviors of ECs in response to high-glucose and hypoxic environments and the underlying mechanisms remain unclear. In this study, we investigated the collective migration of ECs simultaneously stimulated by changes in glucose and oxygen concentrations. Cell migration in EC monolayer formed inside the media channels of microfluidic devices was observed while varying the glucose and oxygen concentrations. The cell migration increased with increasing glucose concentration under normoxic condition but decreased under hypoxic condition, even in the presence of high glucose levels. In addition, inhibition of mitochondrial function reduced the cell migration regardless of glucose and oxygen concentrations. Thus, oxygen had a greater impact on cell migration than glucose, and aerobic energy production in mitochondria plays an important mechanistic role. These results provide new insights regarding vascular homeostasis relative to glucose and oxygen concentration changes.

Liquid atomization technology is one of the applications in various fields of modern industry because it improves reactivity, diffusion, and permeability of liquids. However, existing atomization technologies are severely limited by the physical and chemical properties of the solution or the object to be treated, and there is a growing need to develop atomization technologies that solve these problems. We have developed a device that atomizes liquids to the nanoscale based on the interaction with a dielectric barrier discharge, which enables the atomization of various types of solutions, including water-based and oil-based solutions. Herein, we report the results of visualizing the dynamics of liquid atomization using a high-speed camera. The device atomizes solutions in three modes: instability of the solution jet; physical fragmentation of the solution droplets by the impact of the plasma streamer; and collapse of the droplet surface and generation of a smoke-like mist during the streamer ejection from the solution droplet. The combined and repeated action of these three modes on the produced microdroplets is expected to result in nano-sized mists of the solution.

Regenerative medicine is moving from the nascent to the transitional stage as researchers are actively engaged in creating mini-organs from pluripotent stem cells to construct artificial models of physiological and pathological conditions. Currently, mini-organs can express higher-order functions, but their size is limited to the order of a few millimeters. Therefore, one of the ultimate goals of regenerative medicine, “organ replication and transplantation with organoid,” remains a major obstacle. Three-dimensional (3D) bioprinting technology is expected to be an innovative breakthrough in this field, but various issues have been raised, such as cell damage, versatility of bioink, and printing time. In this study, we established a method for fabricating, connecting, and assembling organoid units of various shapes independent of cell type, extracellular matrix, and adhesive composition (unit construction method). We also fabricated kidney tissue-like structures using three types of parenchymal and interstitial cells that compose the human kidney and obtained findings suggesting the possibility of crosstalk between the units. This study mainly focuses on methods for reproducing the structure of organs, and there are still issues to be addressed in terms of the expression of their higher-order functions. We anticipate that engineering innovation based on this technique will bring us closer to the realization of highly efficient and rapid fabrication of full-scale organoids that can withstand organ transplantation.

Engineered three-dimensional (3D) tissue culture platforms are useful for reproducing and elucidating complex in vivo biological phenomena. Spheroids, 3D aggregates of living cells, are produced based on physicochemical or microfabrication technologies and are commonly used even in cancer pathology research. However, conventional methods have difficulties in constructing 3D structures depending on the cell types, and require specialized techniques/lab know-how to reproducibly control the spheroid size and shape. To overcome these issues, we have developed a fabrication method, which enables anyone to make and mature cancer spheroids using a superhydrophobic microwell made of the monolithic porous materials. Here, we characterize the biological behaviors of the breast cancer spheroids fabricated by our method under normoxic and hypoxic conditions. We found that the fabricated spheroid contracted to a certain size via activation of the actomyosin system. Cell proliferation induced a hypoxic state inside the spheroid (elevated expression of the hypoxia-inducible factor HIF-1α), followed by the formation of a necrotic core and cell escape from the spheroid. In addition, we observed a decrease in cancer spheroid contractility and cell escape from spheroids under hypoxic conditions compared to normoxic conditions, which were related to oxygen concentration-dependent cell motility. The fabricated spheroids perform as 3D tumor tissues in a highly reproducible manner and within a short culture period. Our findings indicate that this fabrication method has a wide range of applications in cancer research, such as elucidating the mechanisms of tumor invasion and metastasis and screening anticancer drugs, as with previous methods.

Cell counting is one of the basic and essential procedures that researchers in cell biology, bioengineering, and other related fields learn at the outset. Systems based on various measurement principles are commercially available, and each has its own advantages and disadvantages in terms of performance, cost, and footprint. Herein, we developed a cost-effective, scalable, and compact module that enables cell counting with reasonable accuracy, throughput, and sensitivity. This cell counting module had a size of 29 × 48 × 16 mm and a cost of $165 USD. The module can be assembled by simply inserting commercially available optical and electronic components into a housing printed by CNC milling and soft lithography. To take full advantage of this module, we built an automated cell counting system using open-source and commercially available development platforms. The module exhibited a measurement accuracy (i.e., guaranteed accuracy in the concentration range of 0-500 cells/µL) and sorting resolution (i.e., selection of particles with diameters of 5 µm and 15 µm) tolerable for cellular experiments. This low-cost and small-size module can be a sufficient replacement for a routine system in cell experiments. We anticipate our work will benefit research fields such as cell biology and bioengineering.

One way to ensure the reproducibility of cell experiments is to automate the workflow, which can be achieved using microfluidic device technology. However, microfluidic device technology is only used in a few studies because it requires a lot of time and money, in addition to the know-how needed to develop the technology. In this study, modular microfluidic devices that are inexpensive and freely combinable were developed by integrating micromilling and soft lithography technologies, and the performance of a prototype cell counting device was evaluated. The combination of such single-function devices (modules) and the use of machine learning is expected to improve the efficiency of microfluidic device development.

Vascular endothelial cells (ECs) respond to mechanical stimuli caused by blood flow to maintain vascular homeostasis. Although the oxygen level in vascular microenvironment is lower than the atmospheric one, the cellular dynamics of ECs under hypoxic and flow exposure are not fully understood. Here, we describe a microfluidic platform for the reproduction hypoxic vascular microenvironments. Simultaneous application of hypoxic stress and fluid shear stress to the cultured cells was achieved by integrating a microfluidic device and a flow channel that adjusted the initial oxygen concentration in a cell culture medium. An EC monolayer was then formed on the media channel in the device, and the ECs were observed after exposure to hypoxic and flow conditions. The migration velocity of the ECs immediately increased after flow exposure, especially in the direction opposite to the flow direction, and gradually decreased, resulting in the lowest value under the hypoxic and flow exposure condition. The ECs after 6-h simultaneous exposure to hypoxic stress and fluid shear stress were generally aligned and elongated in the flow direction, with enhanced VE-cadherin expression and actin filament assembly. Thus, the developed microfluidic platform is useful for investigating the dynamics of ECs in vascular microenvironments.

Cancer metastasis remains largely unexplored, despite remarkable advances in treatment technology. Three-dimensional cultures (spheroids) are being used to attempt to reproduce cancer tissue, and highly reproducible quantitative experimental techniques are being developed. We have developed a method to easily generate cancer spheroids and control their size. In this study, we analyzed cell proliferation within the spheroids and the dynamics of cells escaping from the spheroids by culturing them under normoxic and hypoxic conditions. Breast cancer cells that escaped from spheroids under hypoxic conditions showed increased proliferation and early metastasis-associated migration, suggesting the possibility of induction and regulation of the metastatic phenotype.

Objective: Reproduce the antihypertensive effect of physical exercise by applying mechanical intervention. Design and method: We conducted animal experiments in which we reproduced mechanical accelerations generated in the head during treadmill running at a moderate velocity. We performed in vitro experiments using cultured cells to determine what type of mechanical force was responsible for the antihypertensive effect of mechanical intervention. We carried out clinical studies to validate the clinical relevance of our findings. Results: Passive head motion in hypertensive rats, which reproduced the mechanical accelerations generated in their heads during treadmill running at a moderate velocity, decreased the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in the rostral ventrolateral medulla (RVLM). This decrease resulted in lowering their blood pressure. Passive head motion generated interstitial fluid movement, which was estimated to exert shearing forces with an average magnitude of < 1 Pa on the cells in the rat medulla. Application of fluid shear stress of relevant magnitudes decreased the AT1R expression in cultured astrocytes, but not in neuronal cells. Furthermore, interference with interstitial fluid movement by hydrogel introduction in the RVLM of hypertensive rats eliminated the ability of passive head motion and treadmill running to decrease their blood pressure and AT1R expression in the RVLM astrocytes. Consistent with these results from animal experiments, vertically oscillating chair riding by hypertensive adult humans, which reproduced the mechanical accelerations generated in their heads during light jogging, lowered their blood pressure. Conclusion: Brain-targeted mechanical intervention can be antihypertensive by modulating the function of RVLM astrocytes through interstitial fluid shear stress.

The mechanisms by which physical exercise benefits brain functions are not fully understood. Here, we show that vertically oscillating head motions mimicking mechanical accelerations experienced during fast walking, light jogging or treadmill running at a moderate velocity reduce the blood pressure of rats and human adults with hypertension. In hypertensive rats, shear stresses of less than 1 Pa resulting from interstitial-fluid flow induced by such passive head motions reduced the expression of the angiotensin II type-1 receptor in astrocytes in the rostral ventrolateral medulla, and the resulting antihypertensive effects were abrogated by hydrogel introduction that inhibited interstitial-fluid movement in the medulla. Our findings suggest that oscillatory mechanical interventions could be used to elicit antihypertensive effects.

Cardiovascular and cerebrovascular diseases based on stenotic lesions are serious problems in the super-aged society. Stent placement has been clinically applied as a minimally invasive treatment for these diseases. However, this procedure has raised new problems such as restenosis and late thrombosis. We have focused on the contact force exerted by the stent on the vessel wall, which causes restenosis, and aim to establish a design theory for a stent that can expand the stenotic area and has an appropriate contact force distribution. In this study, we evaluated the correlation between the stent expansion force, the contact force acting on the vascular wall, and the expanded diameter of the blood vessel. It was confirmed that the expanded diameter of the blood vessel directly depends on the value of the stent expansion force, while the contact force is affected by the hysteresis characteristics of the stent expansion force.