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Triboelectric nanogenerator (TENG) is one of the emerging energy harvesting technologies with the potential to be an alternative energy source. Owing to the various advantages of TENG, such as low cost, simple design, and high applicability, several researchers reported wearable TENG devices that can power electronics by harvesting human motion. However, as the human body has limited movement, the existing wearable TENG devices can only generate low power to turn on the electronics. In this study, a flow ring-based TENG (FR-TENG) is fabricated, which can be applied to wearable devices to generate high voltage and current output by including an opposite charging intermediate layer. By the simulation and experimental results, FR-TENG is optimized to generate a high output, that is, peak open-circuit voltage and closed-circuit current of up to 1020 V and 260 mA, respectively, owing to the electrostatic discharge. By these results, sleeve-type wearable FR-TENG is fabricated which can effectively harvest energy from arm movement. The sleeve-type FR-TENG can generate a high output owing to the working mechanism of FR-TENG; the high output was used to turn on 200 LEDs.

In recent years, the potential of nanobubbles (NBs) for biological activation has been actively investigated. In this study, we investigated the proliferative effects of nitrogen NBs (N-NBs) on fibroblast cells using cell assays with image analysis and flow cytometry. A high concentration of N-NBs (more than 4 × 108 NBs/mL) was generated in Dulbecco’s modified Eagle’s medium (DMEM) using a gas–liquid mixing method. In image analysis, the cells were counted and compared, which showed an 11% increase in cell number in the culture medium with N-NBs. However, in two further cell cytometry analyses, the effect of nanobubbles on cell division was found to be insignificant (approximately 2%); as there is insufficient evidence that N-NB is involved in cell division mechanism, further studies are needed to determine whether NB affects other cellular mechanisms such as apoptosis. This study presents the first successful attempt of directly generating and quantifying N-NBs in a culture medium for cell culture. The findings suggest that the N-NBs in the culture medium can potentially facilitate cell proliferation.

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.

코로나19는 전 세계적으로 사회적, 경제적, 심리적 그리고 다른 모든 면에서 현재 진행형으로 크고 작은 영향을 미치고 있으며 당연히 대학의 교육에도 큰 영향을 가져왔다. 대표적인 것은 전통적인 대면 교육을 포기하고 대체 방안인 비대면 온라인 교육으로 전환한 것이다. 이에 온라인 교육의 특징과 학생들의 반응을 알아보았다. 코로나19의 범세계적 유행이 지나간 후에는 대학 교육에 대한 인식 변화는 필연적일 것이다. 특히, 교 · 강사와 학생들 모두가 온라인 교육의 본질에 대한 이해가 강화되고 깊어지고 있다. 이것은 온라인 교육을 보다 바람직한 방향으로 발전시킬 수 있는 원동력이 될 것이다. 미래에 전통적 대면 교육과 온라인 교육이 조화롭게 융합되어 새롭고 더 우수한 교육 형태로 거듭나기를 기대한다.

Microwells are used in studies to mimic the in vivo environment through an in vitro environment by generating three-dimensional cell spheroids. These microwells have been fabricated in various shapes using different methods according to the research purpose. However, because all microwells up to now have an open top, it has been difficult to culture spheroids of floating cells due to their low density, such as human adipose-derived stem cells (hASCs) that differentiate into adipocytes. Therefore, the labor-intensive hanging droplet method has been mainly used for the study of adipocytes. Here, we introduce a sigma-well, which is a microwell in the shape of the Greek letter sigma (σ) with a roof. Because of its unique shape, the sigma-well is advantageous for the culture of floating cells by reducing cell loss and external interference. The sigma-well was fabricated using the principle of surface tension of polydimethylsiloxane as well as air trapping and thermal expansion. Unlike conventional microwells, because the center of the bottom surface and the inlet of the sigma-well are not located on the same line and have a difference of approximately 218 μm, the spheroids are cultured more stably and may not escape the cavity. In this study, hASC and adipocyte spheroids differentiated using these sigma-wells were successfully cultured. In addition, through cytokine diffusion simulation, it was confirmed that the diffusion and mass transfer in the sigma-well was lower than that in the conventional microwell. It is expected that the morphological features of the sigma-well, which cannot be easily obtained by other methods, can be beneficial for the study of buoyant cell types such as adipocytes.

Dickkopf-3 (DKK3), a tumor suppressor, is frequently downregulated in various cancers. However, the role of DKK3 in ovarian cancer has not been evaluated. This study aimed to assess aberrant DKK3 expression and its role in epithelial ovarian carcinoma. DKK3 expression was assessed using immunohistochemistry with tissue blocks from 82 patients with invasive carcinoma, and 15 normal, 19 benign, and 10 borderline tumors as controls. Survival data were analyzed using Kaplan–Meier and Cox regression analysis. Paclitaxel-resistant cells were established using TOV-21G and OV-90 cell lines. Protein expression was assessed using Western blotting and immunofluorescence analysis. Cell viability was assessed using the MT assay and 3D-spheroid assay. Cell migration was determined using a migration assay. DKK3 was significantly downregulated in invasive carcinoma compared to that in normal, benign, and borderline tumors. DKK3 loss occurred in 56.1% invasive carcinomas and was significantly associated with disease-free survival and chemoresistance in serous adenocarcinoma. DKK3 was lost in paclitaxel-resistant cells, while β-catenin and P-glycoprotein were upregulated. Exogenous secreted DKK3, incorporated by cells, enhanced anti-tumoral effect and paclitaxel susceptibility in paclitaxel-resistant cells, and reduced the levels of active β-catenin and its downstream P-glycoprotein, suggesting that DKK3 can be used as a therapeutic for targeting paclitaxel-resistant cancer.

In recent years, extremely small gas bubbles called bulk nanobubbles (BNBs) have drawn great attention due to their impressive effects and their wide applicability in a variety of technological fields, including biomedical engineering, water treatment, and nanomaterials. However, unsolved questions remain regarding the stability and behavior of BNBs. In the present work, BNBs were generated in water using a gas-liquid mixing method. To investigate the coarsening behavior of BNBs in water over time, particle analysis was performed using a nanoparticle tracking analysis (NTA) method. Over time, the BNB diameter continuously increased (from 88.50 nm to 201.00 nm), and its cubic radius increased linearly (r3 ~ t). While the concentration of BNBs decreased (from 3.47 ×108 particles/mL to 0.61 ×108 particles/mL), the total volume of BNBs remained the same. Moreover, the size distribution broadened over time, and the concentration of larger BNBs gradually increased over time. These results indicate that relatively small BNBs disappear and larger BNBs grow through mass transfer between BNBs instead of dissolution of the gas and coalescence. In other words, BNBs underwent Oswald ripening; that is, gas molecules detached from smaller BNBs, diffused into the continuous phase, and then were absorbed into larger BNBs.

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.

In recent years, the potential of nanobubbles (NBs) for biological activation has been actively investigated. In this study, we investigated the proliferative effects of nitrogen nanobubbles (N-NBs) on fibroblast cells using cell assays with image analysis and flow cytometry. A high concentration of N-NBs (more than 4 × 108 NBs/mL) was generated in Dulbecco’s modified Eagle’s medium (DMEM) using a gas-liquid mixing method. In image analysis, the cells were counted and compared, which showed an 11% improvement in proliferation in the culture medium with N-NBs. In flow cytometry, the decrease in the fluorescence intensity was analyzed, which revealed a 1.5% improvement in proliferation in the culture medium with N-NBs. This study represents the first successful attempt of directly generating quantified NBs in a culture medium for cell culture. The findings suggest that the N-NBs in the culture medium can facilitate cell proliferation.

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.

Metallic bone-fixation devices have been widely used in the treatment of fractured bones. However, there are still some unmet clinical needs associated with post-surgical infection and hampered bone repair. Therefore, to both prevent infection and enhance bone formation, we propose a titanium (Ti)-based bone plate for dual delivery of an antibiotic, vancomycin (VAN), and a bone-forming drug, alendronate (AL). In this work, we prepared the coating with a blend of a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), and a drug, VAN or AL. Instead of coating the whole surface, we patterned the coatings each in the shape of a dot, on a flat surface of the Ti bone plate currently in clinical use (BP0001-PT, U&I, Korea). This way, we could prevent detachment of the polymeric coating from the metallic plate surface while being immersed in an aqueous medium for 23 days. Both VAN and AL were released in a sustained manner for more than 28 days, maintaining their own activity without being influenced by their co-existence in the medium. Thus, the coated plate showed an antibacterial activity against Staphylococcus aureus, while also promoting osteoblast proliferation and alkaline phosphate activity in MG-63 cells. Therefore, we conclude that a Ti-based bone plate coated with patterned dots, each for delivery of VAN or AL, can be a promising strategy to allow for both antibacterial and bone-forming activities.

Human cells encounter a range of shear stress levels in situ and this natural variability in shear stress implies that realistic investigations of cell type characteristics may depend on nontrivial shear stress models. Human adipose-derived stem cells (hASCs) differentiate near the blood capillary vessels where interstitial flows predominate. However, the effects of interstitial levels of shear on hASCs are not fully understood. In this study, we propose a microfluidic shear generation system, in which a gradient distribution of the interstitial level of shear flow is created to investigate the effects of interstitial-level shear flow on hASCs. To generate such a gradient profile of interstitial-level shear stress, we fabricated a semicircle-shaped microfluidic channel, and generated an extremely low flow using an osmosis-driven pump. Changes to hASC morphology, proliferation, and differentiation were observed under shear stresses of 1.8 × 10-3-2.4 × 10-3 Pa. At higher shear stresses, we found higher proliferation rates, stronger actin structures, and lower differentiation. We also conducted computational simulations of a monolayer culture, which showed that the shear stress level even on a single cell varies owing to the change of the cell thickness between the pseudopodia and the nucleus. We found that hASCs detectably respond to extremely low levels of shear flow, above a threshold of ∼2.0 × 10-3 Pa. Our microplatform may be useful for quantitating biological responses and function changes of other stem cells and cancer cells to interstitial-level shear flows.

A three-dimensional spheroid cell culture can obtain more useful results in cell experiments because it can better simulate cell microenvironments of the living body than two-dimensional cell culture. In this study, we fabricated an electrical motor-driven lab-on-a-CD (compact disc) platform, called a centrifugal microfluidic-based spheroid (CMS) culture system, to create three-dimensional (3D) cell spheroids implementing high centrifugal force. This device can vary rotation speeds to generate gravity conditions from 1 x g to 521 x g. The CMS system is 6 cm in diameter, has one hundred 400 μm microwells, and is made by molding with polydimethylsiloxane in a polycarbonate mold premade by a computer numerical control machine. A barrier wall at the channel entrance of the CMS system uses centrifugal force to spread cells evenly inside the chip. At the end of the channel, there is a slide region that allows the cells to enter the microwells. As a demonstration, spheroids were generated by monoculture and coculture of human adipose-derived stem cells and human lung fibroblasts under high gravity conditions using the system. The CMS system used a simple operation scheme to produce coculture spheroids of various structures of concentric, Janus, and sandwich. The CMS system will be useful in cell biology and tissue engineering studies that require spheroids and organoid culture of single or multiple cell types.

The solar updraft tower (SUT) is a renewable power generation system that uses natural air convection from the ground that is heated by solar radiation. Placing flow-guide structures within the collector of the SUT can enhance aerodynamic performance, and hence, increase the kinetic power. Here, we propose a central guide post (CGP) structure in the SUT that controls updraft flow. The effect of the CGP geometry on aerodynamic performance was investigated using computational fluid dynamics modeling (ANSYS Fluent 19.2) to show that a CGP can play a positive role by preventing stagnation of the airflow at the center of the collector, resulting in increased kinetic power output (up to ~2%). However, excessively long CGPs retarded airflow, resulting in a dramatic decrease in kinetic power output. We also investigated a system with both a CGP (to improve aerodynamic performance and minimize energy loss) and a heat-exchange baffle (to maximize thermal energy transfer). When installed with a proper distance between components, the CGP and baffle showed a combined effect of increasing the kinetic power output by up to 10%. We expect that our proposed method using the CGP and baffle system will contribute to the development of better future SUT technology.

Polydimethylsiloxane (PDMS) membranes are used in various applications, such as microvalves, micropumps, microlenses, and cell culture substrates, with various thicknesses from microscale to nanoscale. In this study, we propose a simple fabrication method for PDMS membranes on a water surface, referred to as the floating-on-water (FoW) method. FoW can be used to easily fabricate PDMS membranes with thicknesses of a few micrometers (minimum 3 &mu, m) without special equipment. In addition, as the membrane is fabricated on the water surface, it can be easily handled without damage. In addition, alternative membrane structures were demonstrated, such as membrane-on-pins and droplet-shaped membranes. FoW can be widely used in various applications that require PDMS membranes with microscale thicknesses.

The rim seal of the gas turbine is intended to protect the material of the turbine disk from hot combustion gases. The study of the rim seal structure is important to minimise the coolant flow and maximise the sealing effect. In this paper, a wave-shaped rim seal for stator disks is proposed and its effect is confirmed by numerical analysis. To characterise the flow phenomena near the wave-shaped rim seal, a simplified model of the wave-shaped rim seal (Type 1 model), which excludes the rotor blade and stator vane, is analysed and compared with the conventional rim seal. Then, through analysis of the wave-shaped rim seal geometry (Type 2 model), which includes the rotor blade and stator vane, a reduction in egress and ingress flow was observed owing to the wave-shaped rim seal, and the sealing effectiveness on the stator disk of turbine was increased by up to 3.8%. Implementation of the wave-shape geometry in the radial seal is a novel choice for turbine designers to consider in future for better-performing and more-efficient turbines.

Three-dimensional (3D) in vitro model systems such as spheroids and organoids provide an opportunity to extend our physiological understanding using recapitulated tissues that mimic physiological characteristics of in vivo microenvironments. Unlike two-dimensional (2D) systems, 3D in vitro systems can bridge the gap between inadequate 2D cultures and the in vivo environments, providing novel insights on complex physiological mechanisms at various scales of organization, ranging from the cellular, tissue-, to organ-levels. To satisfy the ever-increasing need for highly complex and sophisticated systems, many 3D in vitro models with advanced microengineering techniques have been developed to answer diverse physiological questions. This review summarizes recent advances in engineered microsystems for the development of 3D in vitro model systems. We highlight and discuss in detail the relationship between the underlying physics behind the microengineering techniques, and their ability to recapitulate distinct 3D cellular structures and functions of diverse types of tissues and organs. We also introduce a number of 3D in vitro models and their engineering principles. Finally, we summarize current limitations, and provide perspectives for future directions in guiding the development of 3D in vitro model systems using microengineering techniques.

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.

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 (&theta, ) 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 &theta, value was 105&deg, at which the AC voltage was improved by 7.4% compared to that in the case of the basic model with &theta, = 0&deg, The maximum electric power output was 9.333 &mu, W and the load resistance was 47.62 k&Omega, 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.

Differentiation of stem cells into chondrocytes has been studied for the engineering of cartilage tissue. However, stem cells cultured two-dimensionally have limited ability to differentiate into chondrocytes, which led to the development of three-dimensional culture systems. A recently developed microtechnological method uses microwells as a tool to form uniformly sized spheroids. In this study, we fabricated an array (10 × 10) of goblet-shaped microwells based on polydimethylsiloxane for spheroid culture. A central processing unit (CPU) was used to form holes, and metallic beads were used to form hemispherical microwell geometry. The holes were filled with Pluronic F-127 to prevent cells from sinking through the holes and allowing the cells to form spheroids. Viability and chondrogenic differentiation of human adipose-derived stem cells were assessed. The fabrication method using a micro-pin mold and metallic beads is easy and cost-effective. Our three-dimensional spheroid culture system optimizes the efficient differentiation of cells and has various applications, such as drug delivery, cell therapy, and tissue engineering.

Solar updraft towers (SUTs) are used for renewable power generation, taking advantage of the thermal updraft air flow caused by solar energy. Aerodynamic devices have been applied to SUTs to improve their performance and the baffle is one such device. Here, we investigate the effect of baffle installation on the thermo-fluid dynamic phenomena in the collector of an SUT and how it enhances the overall SUT performance using computational fluid dynamics analysis. Two geometric parameters (height and width of baffle) and two thermal boundary conditions of the baffle (adiabatic condition and heat flux condition) were tested through simulations with 10 different models. The vortex generated by the baffle has a positive effect on the delivery of heat energy from the ground to the main flow, however, one disadvantage is that the baffle inherently increases the resistance of the main flow. Over 3% higher kinetic power was achieved with some of the simulated baffle models. Therefore, an optimum design for baffle installation can be achieved by considering the positive and negative thermo-fluid dynamics of baffles.

A cell spheroid culture has the benefit of simulating in vivo three-dimensional cell environments. Microwell systems have been developed to mass-produce large quantities of uniform spheroids, and are frequently used in research areas, such as cell biology, anticancer drug development, and regenerative therapy. Recently reported concave-bottomed microwell systems have delivered more benefits in producing spheroids of higher quality and facilitating more effective research. However, microwell fabrication methods are often complicated or expensive, and there are inherent limitations in the functions and characteristics of existing microwells. Therefore, further studies on concave microwell systems are required. In this study, we fabricate spherical microwells with funnel-shaped entrance structures for spheroid culture; the shape is an upside-down omega ([Formula: see text]), and is thus named 'Omega-well'. The Omega-well array is fabricated using the capillary action of liquid polymer on the pins of a computer central processing unit, which is accomplished without requiring expensive materials or difficult procedures. Various characteristic analyses are performed by experiments and computer simulation. It is demonstrated that cell loss is minimized during cell seeding, a produced spheroid does not easily escape, and that crosstalk between microwells is significantly reduced. The novel fabrication method and Omega-well platform proposed in this study are highly practical, and thus will be useful tools in biology and pharmaceutical labs.

A spheroid culture is a useful tool for understanding cellular behavior in that it provides an in vivo-like three-dimensional environment. Various spheroid production methods such as non-adhesive surfaces, spinner flasks, hanging drops, and microwells have been used in studies of cell-to-cell interaction, immune-activation, drug screening, stem cell differentiation, and organoid generation. Among these methods, microwells with a three-dimensional concave geometry have gained the attention of scientists and engineers, given their advantages of uniform-sized spheroid generation and the ease with which the responses of individual spheroids can be monitored. Even though cost-effective methods such as the use of flexible membranes and ice lithography have been proposed, these techniques incur serious drawbacks such as difficulty in controlling the pattern sizes, achievement of high aspect ratios, and production of larger areas of microwells. To overcome these problems, we propose a robust method for fabricating concave microwells without the need for complex high-cost facilities. This method utilizes a 30 x 30 through-hole array, several hundred micrometer-order steel beads, and magnetic force to fabricate 900 microwells in a 3 cm x 3 cm polydimethylsiloxane (PDMS) substrate. To demonstrate the applicability of our method to cell biological applications, we cultured adipose stem cells for 3 days and successfully produced spheroids using our microwell platform. In addition, we performed a magnetostatic simulation to investigate the mechanism, whereby magnetic force was used to trap the steel beads in the through-holes. We believe that the proposed microwell fabrication method could be applied to many spheroid-based cellular studies such as drug screening, tissue regeneration, stem cell differentiation, and cancer metastasis.

The engineered three-dimensional (3D) cell cultivation system for the production of multicellular spheroids has attracted considerable attention due to its improved in vivo relevance to cellular communications compared with the traditional two-dimensional (2D) cell culture platform. The formation and maintenance of cell spheroids in a healthy condition is the critical factor for tissue engineering applications such as the repair of damaged tissues, the development of organ replacement parts and preclinical drug tests. However, culturing spheroids in conventional isolated single wells shows limited yield and reduced maintenance periods due to the lack of proper supplies of nutrition as well as intercellular chemical signaling. Here, we develop novel networked concave microwell arrays for the effective construction of 3D multi-cellular spheroids. The proposed method provides a suitable structure for the diffusion of oxygen, water-soluble nutrients and cytokines for cell-cell interactions between the spheroids in neighboring microwells. We have further demonstrated that hepatocyte spheroid cultured networked concave microwells show enhanced cell viability and albumin secretion compared to the un-networked control group over two weeks. Our results reveal that multi-cellular functionality can be tuned up by networking individual 3D spheroids without supplying additional chemicals or biological supplements. We anticipate our result to be useful in high-throughput cellular screening platforms to study cell-cell interactions, in response to diverse chemical stimuli as well as the development of the in vivo mimicking of the customized 3D tissue culture system.

Background The human airway is exposed to the development of diverse flow patterns based on differences in its morphological/geometrical parameters across individuals. Although effects of the asymmetry between the right and left main bronchi on airway flows have been investigated in the past, there exists a paucity in terms of studies that focus on the role of stronger physiological asymmetric features, such as off-plane bifurcation angles of primary bronchi, in expiratory flows. Method Computational fluid dynamic techniques have been used to demonstrate presence of Dean-type secondary flows and vortices in the bifurcation region. Formation of a distinctive pattern was observed corresponding to an increase in the off-plane branching angle. An experiment involving 3D printed airways and smoke was also performed to visualize flow patterns and verify simulation results. Results Good agreement was observed between computational and experimental results. Furthermore, it was revealed that the predicted wall shear stress distribution demonstrated significant changes (with a maximum shear stress increase of 30.7%) compared to conventional airway models that adopt symmetric bifurcation angles. The overall flow demonstrated a swerving motion, which was characterized by tracking the vortex cores (maximum accumulated radial movement of 72.6°) when they ascended towards the trachea inlet in off-plane airway models. Conclusions It was confirmed that off-plane bifurcations in human trachea significantly alter the flow characteristics in expiratory flows. It is expected that the results of this study will provide useful information regarding increasingly advanced patient-specific treatments for respiratory diseases in the trachea.

In living tissue, cells exist in three-dimensional (3D) microenvironments with intricate cell-cell interactions. To model these cellular environments, numerous techniques for generating cell spheroids have been proposed and improved. However, previously reported methods still have limitations in uniformity, reproducibility, scalability, throughput, etc. Here, we present a centrifugal microfluidic-based spheroid (CMS) formation method for generating both co-culture and mono-culture 3D spheroids in a highly controlled manner. We designed circularly arrayed microwells to allow the even distribution of cells introduced at the center of a rotating platform and to provide identical hypergravity conditions at each well by the centrifugal forces generated. Compared with conventional well plate-based spheroid formation, the CMS formation method significantly promotes sphericity and consistency in both size and shape with high production yields. In addition to mono-culture spheroids, we successfully generated co-culture spheroids in concentric, Janus, and sandwich shapes using human adipose-derived stem cells and human lung fibroblasts, demonstrating the versatility of our CMS formation method. We believe that our new method for generating 3D spheroids will become one of the essential technologies in the field of 3D cell culture. We also expect that we are providing an innovative means to assess cellular responses, including cell motility under different hypergravity conditions.

The solar updraft tower (SUT) is a renewable power generation system that uses the natural convection phenomenon of the ground&rsquo, s air heated by solar radiation. The baffle is a thermo-fluid dynamic structure that improves the heat exchange efficiency and has been recently reported to be a useful tool to increase the output of the SUT. However, one of the less well-known issues is the relationship between the thermo-fluid dynamic characteristics of the flow in the collector of the SUT and the installation location of the baffle and how this affects the power output and SUT efficiency. In this study, the positive and negative thermo-fluid dynamic effects of the baffle, which vary depending on the installation location, are quantitatively analyzed, and the best location is predicted where the overall kinetic power generated by the SUT is maximized. The target SUT model consists of a chimney (12 m height and 0.25 m diameter) and a collector (1 m height and 10 m diameter), and a total of eight model cases are calculated. The results confirm that the kinetic power is lower or higher than that of the control model having no baffle, depending on the baffle installation location. When the position of the baffle is 4.5 m from the center, the increase in kinetic power is maximized by 8.43%. Two important conclusions are that the baffle should interfere minimally with the progress of the main flow into the chimney, generating kinetic power, and at the same time, the baffle should isolate the inner recirculating flow in order to accumulate the heat in the collector so that the natural convection strength is maximized. The perspective gained from the resulting data is useful for SUT design and for pursuing a higher efficiency in the future.

Traditional cell culture methods allow bulk biomolecular assays; however, individual cell responses are blended, lost, and ignored. To overcome such limitations of the traditional cell culture methods and to provide more in vivo-like microenvironments, a microwell array system has been used in the last few decades as a very attractive tool for analyzing individual cells. The basic cell trapping mechanism of a microwell system is simple; cells drop into the microwell by gravity. However, there are demands for advanced microwell systems that are capable of performing more active functions. Innovations in substrate materials and cell trapping/handling mechanisms used for microwell systems are meeting such needs. This paper presents an overview of various microwell fabrication techniques, cell trapping mechanisms, and biological applications. Future innovations in microwell systems, which will be useful for cell biology, tissue engineering, and biomedical engineering, are also explored.

Spheroid cell culture is very useful for further understanding cellular behavior including motility and biochemical reaction since it mimics three-dimensional (3D) in vivo organ tissue. Among previously proposed various methods for spheroid production, such as hanging drop and spinner flask, microwell is a recently developed method harnessing microtechnology to produce uniform-sized spheroids. Although soft-lithography has been popular for creating microwell arrays, a 3D spherical geometry has been regarded as difficult to fabricate using conventional methods, or often requires complex fabrication processes and expensive equipment. Here, we propose a new method for fabricating concave microwells for cell spheroid production and culture. To demonstrate this method, we fabricated a 30 × 30 microwell array in 3 × 3 cm plates, utilizing metal beads, a through-hole array, and an assembly of small magnets. The spherical metal beads were used as a mold for the microwell, naturally creating the desired 3D concave microwell geometry. One of the key ideas was to place and hold each metal bead in the designated through-hole using the small magnet array. We also performed computational simulation of the magnetostatic force to design and observe the magnetic force field in detail. In addition, to provide a practical demonstration of the proposed system in cell biology, we created and cultured adipose-derived stem cell spheroids for 14 days for chondrogenic differentiation. This method allows further variations in microwell geometry that will enhance the method's applicability as a helpful tool for various studies in cell biology, cancer research, and tissue engineering.