Traditional two-dimensional (2D) cell cultures often fail to replicate the complex three-dimensional (3D) microenvironments foundin vivo, where cells interact with biochemical and mechanical cues. Emerging 3D co-culture platforms better mimic intercellular interactions, cellular differentiation, and drug responses; however, existing methods-such as hydrogel encapsulation and hanging droplets-face challenges in accessibility, scalability, and ease of use. This paper presents the Swivel Microwell, a novel platform that enables efficient spheroid pairing through a simple rotational mechanism. The device, fabricated using computerized numerical control-machined poly(methyl methacrylate) (PMMA) molds and by casting polydimethylsiloxane (PDMS), utilizes gravity, surface tension, and hydrostatic pressure to facilitate spheroid assembly without the need for specialized equipment. Controlled air bubble nucleation guides precise microwell formation, allowing custom well structures on multiple surfaces. Experimental and numerical analyses confirm the platform's ability to generate multiple spheroid pairs and demonstrate its potential for high-throughput applications. The design is expected to support complex co-culture systems, including 2D-3D hybrids and multispheroid assemblies when modified. The Swivel Microwell offers an accessible, scalable, and versatile tool for dynamic spheroid manipulation, opening new possibilities for tissue engineering, drug screening, and cellular biology research.

Blowers, essential for aerator operation, are pivotal mechanical devices that induce airflow through an impeller. Extensive research has explored impeller geometrical parameters, such as size, angle, and blade count. However, limited attention has been paid to the synergic effect of optimizing the bell mouth of the blower inlet and the nose cone of the impeller eye. This study utilized computational fluid dynamics (CFDs) to analyze the impact of the bell mouth and nose cone on the blower through a geometric case study and evaluate the synergy between these components. A bell mouth decreases the wake by 91.76%, and a nose cone decreases the stagnation at the impeller eye and expands the effective impeller area by 76.29%. Moreover, this study demonstrated a significant synergistic effect between the bell mouth and nose cone, which reduced the head loss by 81.4% compared with the base model. This study presents a simple and effective method to improve blower efficiency and reduce power consumption by applying aerodynamically designed bell mouths and nose cones to blowers.

Critical limb ischemia (CLI), an advanced stage of peripheral arterial disease, is identified by severe ischemia, rest pain, and tissue necrosis, and possibly leads to amputation if untreated. Cell therapies offer treatment options for CLI by alleviating resting pain and improving the condition of damaged tissues. However, it may mediate immune rejection reactions after cell transplantation and cell activities are susceptible to environmental influences. Small extracellular vesicles (sEV) have emerged as a promising approach for the treatment of CLI, as these carry a lot of the active substances of cells during their formation process. In this study, we investigated the potential of small extracellular vesicles secreted by interstitial cells (IC-sEV) to restore tissue functions and repair ischemic tissue. Our results demonstrated that IC-sEV could effectively promote the proliferation, migration and tube formation of HUVECs. Moreover, IC-sEV had a more pronounced effect on promoting the expression of angiogenic factors in HUVECs compared to ASC-sEV. The therapeutic effect of IC-sEV was further investigated using an in vivo animal model of limb ischemia. These data demonstrated that IC-sEV significantly improved blood perfusion in ischemic limbs, promoted the recovery of limb functions, and reduced the extent of ischemic tissue damage. Further analysis revealed that IC-sEV promoted microvascular densities, markedly decreased infiltration, cell apoptosis and fibrosis in the ischemic limbs. In conclusion, IC-sEV transplantation is expected to become a new alternative for the treatment of CLI.

A solar updraft tower (SUT) is a power-generating structure that transforms solar energy into electricity through the kinetic energy of air rising due to solar-radiation-induced buoyancy. In traditional architecture, a vestibule is a small room that leads to the main room, and it separates the indoor and outdoor atmospheres, thereby reducing heat loss and improving the thermal performance of the main room. Herein, we propose a canopy-attached divider structure that can create a vestibule-like space and increase the overall thermo-fluid dynamic efficiency of SUTs. A computer simulation study was conducted for various divider geometries in terms of their locations and shapes to create diverse vestibules. The control parameters were the gap between the divider tip and the ground and the length along the radial direction, which determines the vestibule volume. SUT efficiency was analyzed using the velocity, temperature, and turbulence kinetic energy (TKE) contours obtained herein. The vestibule created by installing a divider with a gap of 60 mm and a length of 4.6 m can increase the outlet velocity by up to 6.97 %. The study demonstrated that integrating the well-established technology of the 'vestibule' with the SUT resulted in enhanced performance, showcasing a synergy between the conventional approach and the innovative SUT.

Hair loss caused by malfunction of the hair follicle stem cells (HFSCs) and physical damage to the skin is difficult to recover from naturally. To overcome these obstacles to hair follicle (HF) regeneration, it is essential to understand the three-dimensional (3D) microenvironment and interactions of various cells within the HFs. Therefore, 3D cell culture technology has been used in HF regeneration research; specifically, multicellular spheroids have been generally adapted to mimic the 3D volumetric structure of the HF. In this study, we culture HF-derived cells, which are mainly composed of HFSCs, in the form of 3D spheroids using a microwell array and discuss the effects of the 3D cellular environment on HF morphogenesis by expression measurements of Sonic hedgehog signaling and stem cell markers in the HF spheroids. Additionally, the influences of microwell depth on HF spheroid formation and biological conditions were investigated. The biomolecular diffusion and convective flow in the microwell were predicted using computational fluid dynamics, which allows analysis of the physical stimulations occurring on the spheroid at the micro-scale. Although a simple experimental method using the microwell array was adopted in this study, the results provide fundamental insights into the physiological phenomena of HFs in the 3D microenvironment, and the numerical analysis is expected to shed light on the investigation of the geometric parameters of the microwell system.

Over the past few decades, research on life in space has increased. Owing to the expensive nature of and the challenges associated with conducting experiments in real space, clinostats, which continuously randomize the gravity vector by using motors, have been used to generate simulated microgravity (SMG) on Earth. Herein, by using a 3D printing method, we develop a customized small-sized clinostat (CS clinostat) that is easy to manufacture, inexpensive, and robust. Moreover, we develop and fabricate a gas-permeable polydimethylsiloxane culture dish that fits inside the CS clinostat. To validate SMG generation, ovarian cancer cells (OV- 90, TOV-21G, and Caov-3) were applied to demonstrate a significant reduction in caveolin-1 expression, a biomarker of SMG, indicating SMG generation. The proposed CS clinostat system has good accessibility for SMG research, which makes it useful as a tool for biologists, who are unfamiliar with conventional clinostat equipment, to conduct preliminary studies in the space environment.

Abstract Over the past few decades, research on life in space has increased. Owing to the expensive nature of and challenges associated with conducting experiments in real space, clinostats, which create rotational motion by using motors to reduce the effect of gravity, are used to generate simulated microgravity (SMG) on Earth. However, the existing clinostat systems are complex, large, and expensive, which reduces their accessibility to researchers. Here, by using a 3D printing method, we develop a novel customized small-sized clinostat (CS clinostat) that is easy to manufacture, inexpensive, and robust. The dimensions of the CS clinostat are 282 × 140 × 252 mm3, and therefore, it can fit inside a typical 50 L incubator. The two motors of the CS clinostat rotate at 4 rpm (inner axis) and 1.8 rpm (outer axis) such that the accumulated three-axis acceleration is less than 3 × 10-2 G within 1 h. Moreover, we develop and fabricate a novel culture dish that fits inside the CS clinostat. This dish is covered with polydimethylsiloxane to facilitate gas exchange during cell culture. To validate SMG generation in the CS clinostat, we applied it to mammalian cells, OV-90, TOV-21G, and Caov-3, ovarian cancer cells. Western blotting analysis demonstrated significant reduction in Caveolin-1 expression, a biomarker of SMG, indicating SMG generation. The proposed CS clinostat system has good accessibility and reduces the barriers to SMG research, which makes it useful as a tool for biologists, who are unfamiliar with conventional clinostat equipment, to conduct preliminary studies in the space environment.

Microfluidic devices have emerged as powerful tools for cell-based experiments, offering a controlled microenvironment that mimic the conditions within the body. Numerous cell experiment studies have successfully utilized microfluidic channels to achieve various new scientific discoveries. However, it has been often overlooked that undesired and unnoticed propagation of cellular molecules in such bio-microfluidic channel systems can have a negative impact on the experimental results. Thus, more careful designing is required to minimize such unwanted issues through deeper understanding and careful control of chemically and physically predominant factors at the microscopic scale. In this paper, we introduce a new approach to improve microfluidic channel design, specifically targeting the mitigation of the aforementioned challenges. To minimize the occurrence of undesired cell positioning upstream from the main test section where a concentration gradient field locates, an additional narrow port structure was devised between the microfluidic upstream channel and each inlet reservoir. This port also functioned as a passive lock that hold the flow at rest via fluid-air surface tension, which facilitated manual movement of the device even when cell attachment was not achieved completely. To demonstrate the practicability of the system, we conducted experiments and diffusion simulations on the effect of endocrine disruptors on germ cells. To this end, a bisphenol-A (BPA) concentration gradient was generated in the main channel of the system at BPA concentrations ranging from 120.8 μM to 79.3 μM, and the proliferation of GC-1 cells in the BPA gradient environment was quantitatively evaluated. The features and concepts of the introduced design is to minimize unexpected and ignored error sources, which will be one of the issues to be considered in the development of microfluidic systems to explore extremely delicate cellular phenomena.

As the number of elderly drivers rapidly increases worldwide, interest in the dangers of driving is growing as accidents rise. The purpose of this study was to conduct a statistical analysis of the driving risk factors of elderly drivers. In this analysis, data from the government organization's open data were used for the secondary processing of 10,097 people. Of the 9990 respondents, 2168 were current drivers, 1552 were past drivers but were not driving presently, and 6270 did not have a driver's license; the participants were divided into groups accordingly. The elderly drivers who were current drivers had a better subjective health status than those who were not. Visual and hearing aids were used in the current driving group, and their depression symptoms reduced as they drove. The elderly who were current drivers experienced difficulties while driving in terms of decreased vision, hearing loss, reduced arm/leg reaction speed, decreased judgment of the road conditions such as signals and intersections, and a decreased sense of speed. The results suggest that elderly drivers are unaware of the medical conditions that can negatively affect their driving. This study contributes to the safety management of elderly drivers by understanding their mental and physical status.

Although surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique with unbeaten sensitivity, the capabilities of SERS have been not fully utilized in screening applications because throughput of spectrum detection by conventional Raman instruments has been restricted due to their single-point measurement manners. Hence, this paper presents a development of a high throughput Raman screening system that employs a fiber-optic switch and a Raman probe array. In the system, a 785 nm excitation light is directed into the 1 × 8 broadband optical switching device and selectively switched to one of 8 output ports connected to the corresponding Raman probe array to deliver the light to samples under each probe. This optical switching driven probing in sequence allows us to rapidly detect Raman scattering of the multiple ( n = 8) samples in array within a short time (~ 28 s) with decent sensitivity (10 –7 M). The Raman spectroscopy of the system is validated by comparing the features of Raman spectra obtained from vitamin C tablets with those from a commercial Raman microscope and the detection sensitivity is measured with SERS substrates with different concentrations. Then, feasibility of high throughput screening is tested with a SERS chip array.

With epidemics that have frequently occurred in the 21st century, various diagnostic techniques are being actively researched to replace the public diagnosis tool, DNA amplification technique (Poly-chain reaction, PCR). Among antigen readout techniques, SERS (Surface Enhanced Raman spectroscopy), which can find out the structure of a single molecule level, has received considerable attention as an alternative technique for replacing PCR because this can detect strong signals even with low concentration samples – inducing rapid diagnosis. Despite this advantage, it is still challenging to utilize as a public diagnostic tool due to the inconvenience of continuously replacing samples for measuring a large number of samples. In this study, we developed a SERS-based massive testing system that combined an optical switch and Raman spectroscopy, with simplifying the system to improve portability. In the system, 1xN optical switch, the mechanical displacement of input fiber is moved in a bidirectional way, which makes the input fiber shift into the location corresponding to each output fiber – inducing transmission for the light source and Raman signal. Thus, Raman data of testing samples would be automatically collectible without manual labor like changing specimens for testing another specimen, result ing in rapid diagnostic results for massive samples. We demonstrated the validation of our system by measuring Raman signals for SERS tags.

The motion of organelles inside a cell is an important intrinsic indicator for assessing cell physiology and tissue viability. Dynamic contrast full-field optical coherence tomography (D-FFOCT) is a promising imaging technology that can visualize intracellular movements using the variance of temporal interference signals caused by biological motions. However, double-path interferometry in D-FFOCT can be highly vulnerable to surrounding noise, which may cause turbulence in the interference signals, contaminating the sample dynamics. Therefore, we propose a method for stabilized D-FFOCT imaging in noisy environments by using common-path interferometry in D-FFOCT. A comparative study shows that DFFOCT with the proposed method achieves stable dynamic contrast imaging of a scattering phantom in motion that is over tenfold more noise-insensitive compared to the conventional one, and thus this imaging capability can provide cleaner motion contrast images. With the proposed approach, the intracellular dynamics of biological samples are imaged and monitored.

As an advanced cell culture platform, the organ-on-a-chip has been in the spotlight recently owing to its ability to maintain the physiological characteristics of cells in vitro. Therefore, several disease models have been developed using the organ-on-a-chip technology, and the organ specific three-dimensional (3D) structure and various mechanical/chemical stimuli built into the chip enable efficient development of drugs, medical devices, and biomaterials, as well as realization of patient-specific precise medicine. This study introduces a novel chip-based non-muscle invasive bladder cancer model, multilayered tissue-on-a-chip (MToC), which was created using 3D bio-printing technology, micro-milling, and soft lithography based polydimethylsiloxane (PDMS) casting. All types of cells, T24, MRC-5, and HUVEC, were successfully co-cultured in the MToC. Using computational fluid dynamics (CFD), the flow phenomena occurring in MToC were analyzed. Further, we attempted Bacillus Calmette–Guérin (BCG)-induced migration of THP-1, and the viability reduction of bladder cancer cells and the THP-1 migration were observed. Although follow-up studies are needed to precisely mimic the immune response, this partial phenomenon of the immune response suggests the potential of this device as a surrogate experimental tool for BCG immunotherapy in future.

Iron ore sintering is a pretreatment step of smelting that agglomerates the iron ore using surface melting of green pellets to improve the quality of the steel product. The sintering process not only improves the quality of steel products, but also releases CO and CO2 gases, evaporates moisture, and improves the reducibility of iron ore to ensure smooth operation of the blast furnace. These factors are related with variables such as temperature and flux, so optimization is essential. However, the sintering process generates a lot of cost by consuming the second largest amount of energy in steel manufacturing and releases pollutants, so optimization through experiments is inefficient. Therefore, the various CFD models that simulate the sintering process were developed by the researchers. This paper summarizes the research that developed the iron sintering process as a CFD model. The sintering process is divided into three stages: drying process, reaction process, and cooling process, and the considerations of each study are discussed. We also discuss the strengths and weaknesses of each study. Developing an iron ore sintering model has the potential to extend the application of CFD to the entire steel process, which is expected to reduce cost and environmental impact and increase efficiency.

Stem cell-based therapeutic approach provides a possible treatment for critical limb ischemia (CLI) by inducing revascularization and regenerating ischemic tissue. However, the clinical benefit is modest due to low cell survival and limited efficacy after transplantation. Cardiac-derived stem cells (CSCs) might be a novel cell source for CLI treatment owing to their superb endothelial differentiation potential and angiogenic paracrine functions. In this study, the angiogenic ability of CSCs was maximized by genetic engineering with constitutively active form of hypoxia-inducible factor-1α (CA-HIF-1α), resistant to oxygen-dependent degradation. CSCs transfected with CA-HIF-1α (CA-HIF-CSCs) promoted supplementary expression of proangiogenic factors including VEGF, bFGF, Ang-1 and PDGF-B, along with enhanced angiogenic function including migratory effect, tube formation and endothelial differentiation potential. In the mouse CLI model, CA-HIF-CSCs transplanted into the ischemic region using fibrin gel as cell delivery vehicle, improved blood perfusion and limb functional recovery with minimal incidence of foot necrosis and limb loss by promoting new vessel formation. Histological evidence further confirmed that CA-HIF-CSC/gel treatment markedly alleviated muscle degeneration and fibrosis. CSCs genetically engineered with constitutively active HIF-1α provide a novel therapeutic modality in CLI combining stem cell and gene therapy.

Immunotherapy of bladder cancer is known to have favorable effects, although it is difficult to determine which patients will show a good response because of the different tumor microenvironments (TME). Here, we developed a bladder cancer-on-a-chip (BCOC) to mimic the TME using three-dimensional (3D) bioprinting and microfluidic technology. We fabricated a T24 and a 5637-cell line-based BCOC that also incorporated MRC-5, HUVEC, and THP-1 cells. We evaluated the effects of TME and assessed the immunologic reactions in response to different concentrations of Bacillus Calmette–Guérin (BCG) via live/dead assay and THP-1 monocytic migration, and concentrations of growth factors and cytokines. The results show that cell viability was maintained at 15% filling density in circle-shaped cell constructs at 20 μL/min microfluidic flow rate. A 3D co-culture increased the proliferation of BCOCs. We found that the appropriate time to evaluate the viability of BCOC, concentration of cytokines, and migration of monocytes was 6 h, 24 h, and three days after BGC treatment. Lastly, the immunotherapeutic effects of BCOC increased according to BCG dosage. To predict effects of immunotherapeutic agent in bladder cancer, we constructed a 3D bioprinted BCOC model. The BCOC was validated with BCG, which has been proven to be effective in the immunotherapy of bladder cancer.

Living tissues in the body receive various types of stimuli, including mechanical strain, pressure, and varied chemical environments. In contrast, conventional cell cultures are processed under in vitro conditions, which are not similar to the actual body’s environment. To precisely simulate the human body environment, a dynamic cell culture device capable of applying mechanical stimulation to cells is needed. In this study, an acrylic dielectric elastomer electroactive polymer (EAP), is introduced as a driving component for a dynamic cell culture device with a simple structure. The device is composed of separated upper and lower modules with a driving film at the center, By assembling these components, the electrodes on the surface of the driving film are isolated but still connected by columns that can transfer the deformation of the driving apparatus to the culture membrane. The culturing performance of cells according to the mechanical stimuli was experimentally investigated and compared. Tensile strain was found to provide the highest improvement in cell development rate, reaching up to 32.3%. These results highlight the utility of EAPs for compact and biocompatible dynamic cell culture device design.

Low-intensity winds can be useful power sources in the context of energy harvesting. This study aims to enhance the power generation capacity of a super micro wind turbine (SMWT) in low-intensity winds by modifying the blade geometry, which cannot be realized in conventional wind turbines owing to the stress concentration. By controlling the curved angle (θ) in the middle of the blade, the rotor performance can be improved, and the rotor diameter can be reduced to increase installation density. Experimental results indicated that the optimal θ value was 105°, at which the AC voltage was improved by 7.4% compared to that in the case of the basic model with θ = 0°. The maximum electric power output was 9.333 μW and the load resistance was 47.62 kΩ. Moreover, a computational fluid dynamics analysis was performed to clarify the pressure field and streamlines on and around the blade to demonstrate the aerodynamic performance of the SMWT. The proposed blade geometry is one of many possible designs that can enhance extremely small wind turbines for energy harvesting.

In vivo cells express their characteristics in three-dimensional (3D) microenvironments via cell-cell interactions through autocrine, contact-dependent, paracrine, and synaptic signaling, often between heterologous cell types. Various in vitro 3D microwell-based culture methods have been proposed to further identify cellular characteristics by recreating cellular environments, typically in the form of spheroids and organoids, thereby realizing contact-based cell-cell interactions. However, in vivo cells generally exhibit multiple cellular interaction modes that have not been completely evaluated using existing microwell-based methods. This has led to a demand for more advanced and comprehensive methods. This study introduces a novel apparatus, the membrane-bottomed microwell (MBM) for non-contact co-cultures and 3D cell cultures. The MBM is a combination of a Transwell and a microwell array; these have previously been utilized to facilitate heterologous cell co-culturing and spheroid 3D cell culturing, respectively. In the Transwell insert, the lower part of the MBM is immersed in the culture media in which the cells are being two-dimensionally (2D) cultured, and the spheroids of the MBM are affected by the 2D cultured cells via the membrane at the bottom of the microwell. Here, we describe the methods for manufacturing the MBM in detail and elucidate the results of simulations of diffusion through the bottom of the membrane. We validate the proposed MBM for the spheroid culture of spermatogonial stem cells (SSCs), which had previously been 2D co-cultured with Sandos inbred mouse (SIM)-derived 6-thioguanine- and ouabain-resistant (STO; a mouse embryonic feeder cell line) feeder cells. The proposed system is shown to facilitate successful SSC spheroid culturing with paracrine signaling of STOs through an apparatus that simplifies both the loading and the evaluation processes; therefore, we believe that our findings will enable a more comprehensive understanding of SSCs and associated phenomena and that our system can be applied to various in vitro cell and tissue experiments.

We propose a simple and efficient polydimethylsiloxane (PDMS) double casting method using plasma treatment followed by methanol or ethanol treatment. The plasma treatment oxidizes the functional groups on the surface of the PDMS mold, showing an increase in the concentration of hydroxyl functional groups (OH); subsequent exposure to the alcohols prevents adherence of the second PDMS casting. This process effectively passivates the surface of the PDMS master mold to suppress further chemical bonding. This two-step surface treatment ensures excellent double casting performance at a single micron scale resolution to yield micron level reproduction of objects featuring high aspect ratios, two-dimensional surface micropatterns, and complex three-dimensional microstructures.