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Tissue barriers in a body, well known as tissue-to-tissue interfaces represented by endothelium of the blood vessels or epithelium of organs, are essential for maintaining physiological homeostasis by regulating molecular and cellular transports. It is crucial for predicting drug response to understand physiology of tissue barriers through which drugs are absorbed, distributed, metabolized and excreted. Since the FDA Modernization Act 2.0, which prompts the inception of alternative technologies for animal models, tissue barrier chips, one of the applications of organ-on-a-chip or microphysiological system (MPS), have only recently been utilized in the context of drug development. Recent advancements in stem cell technology have brightened the prospects for the application of tissue barrier chips in personalized medicine. In past decade, designing and engineering these microfluidic devices, and demonstrating the ability to reconstitute tissue functions were main focus of this field. However, the field is now advancing to the next level of challenges: validating their utility in drug evaluation and creating personalized models using patient-derived cells. In this review, we briefly introduce key design parameters to develop functional tissue barrier chip, explore the remarkable recent progress in the field of tissue barrier chips and discuss future perspectives on realizing personalized medicine through the utilization of tissue barrier chips. [ABSTRACT FROM AUTHOR]

Microphysiological system or organ-on-a-chip technologies can replicate the key structure and function of 3D human tissues with higher reproducibility than less controllable 3D cell aggregate models, providing great potential to become advanced drug toxicity and efficacy test platforms alternative to animal models. However, these organ chip models remain to be manufactured and standardized in a highly reproducible manner for reliable drug screening and mechanism of action research. Herein, we present a manufactured form of 'micro-engineered physiological system-tissue barrier chip' called MEPS-TBC for the highly replicable modeling of the human blood–brain barrier (BBB) with a 3D perivascular space. The perivascular region was controlled by tunable aspiration, where human astrocytes reside in 3D, create a network, and communicate with human pericytes facing human vascular endothelial cells, thereby replicating the 3D BBB. The lower channel structure of MEPS-TBC was designed and optimized using a computational simulation to facilitate aspiration while maintaining multicellular construction. Our human BBB model of the 3D perivascular unit and the endothelium perfused by physiological shear stress secured significantly enhanced barrier function exhibiting greater TEER and lower permeability, compared to the only endothelial model, indicating that the cellular interactions between BBB cells significantly contribute to the BBB formation. Importantly, our BBB model showed the cellular barrier function for homeostatic trafficking regulation against inflammatory peripheral immune cells, as well as for molecular transport control across the BBB. We believe our manufactured chip technology will construct reliable and standardized organ-chip models for disease mechanism research and predictive drug screening. [ABSTRACT FROM AUTHOR]

The representative migrant enclave in Beijing, Zhejiangcun, was a 'gray' lawless zone outside the 'red' socialist order from the perspective of the Chinese Communist Party, subject to the government's crackdown and demolition. However, Zhejiangcun surprised everyone by developing into a 'red' space through the grassroots Party-building by its peasant migrant businessmen, starting with the establishment of Beijing's first Party branch of floating Party members in 1995 which now commands 26 Party branches. This article examines this astounding transformation of Zhejiangcun from 'gray' to 'red,' by providing answers to how Zhejiangcun was able to construct and develop a Party organization even before the 'Three Represents' and, in turn, how this Party organization contributed to the success and survival of Zhejiangcun's migrant businessmen. [ABSTRACT FROM AUTHOR]

Medical disorders caused by second-hand smoke are a major public health concern worldwide. To estimate the level of second-hand smoke exposure, salivary diagnostics for cotinine analysis is a compelling alternative in conventional diagnostics using bio-fluids, such as blood and urine, owing to its simple and non-invasive collection method. However, there are several critical issues, such as tedious multisteps, demand for expertise, and field unavailability to collect and transport the purified saliva for further analysis. Here, an all-in-one platform is presented to simply collect real human saliva and directly deliver it onto the biosensing surface. The platform consists of a commercial cotton-swab-type collector, 3D-printed housing, and microfluidic channel integrated with an electrochemical competitive immunosensor to evaluate the level of salivary cotinine. The immunosensor is based on a competitive binding assay between cotinine-conjugated horseradish peroxidase (C-HRP) and cotinine for anti-cotinine binding sites. The current responses obtained from the HRP–thionine–H2O2 system decreased proportionally to the cotinine concentration. This immunosensor successfully detected its target over a range of 1 × 10−1 to 1 × 104 pg ml−1 with a low limit of detection of 6 × 10−2 pg ml−1 and a limit of quantification of 1 × 10−1 pg ml−1. In addition, the platform is applicable to various commercial cotton-swab-type saliva collectors and can successfully transfer the saliva in wide flow rates ranging from 0.1 to 30 ml min−1 without leakage or damage to the sensing surface. Furthermore, the practicality of the proposed platform was evaluated by measuring cotinine in real human saliva from eight non-smokers. The concentration of cotinine was from 45.7 to 890.8 pg ml−1, which was in good agreement with that measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The introduced all-in-one platform represented a reliable performance delivering simple and practical steps in salivary diagnostics. [ABSTRACT FROM AUTHOR]

Bloodstream infection by microorganisms is a major public health concern worldwide. Millions of people per year suffer from microbial infections, and current blood culture‐based diagnostic methods are time‐consuming because of the low concentration of infectious microorganisms in the bloodstream. In this study, we introduce an efficient automated microfluidic system for the continuous isolation of rare infectious bacteria (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) from blood. Bacteria received a balanced force between a fluidic drag force and a periodically controlled dielectrophoretic (DEP) force from tilted electrodes to minimize cell adhesion to the electrodes, which prevented the loss of rare infectious bacteria. Target bacteria were efficiently segregated from the undesired blood cells to ensure that only the bacteria received the DEP force under the hypotonic condition, while the blood cells received no DEP force and exited the channel via a laminar flow. Thus, the bacteria were successfully extracted from the blood with a high recovery yield of 91.3%, and the limit of the bacteria concentration for isolation was 100 cfu/ml. We also developed an automated system that performed every step from blood‐sample loading to application of electricity to the microfluidic chip for bacteria separation. It reduced the standard deviation of the bacteria recovery yield from 6.16 to 2.77 compared with the conventional batch process, providing stable bacteria‐extraction performance and minimizing errors and bacteria loss caused by user mistakes. © 2019 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

3,4-Dihydroxyphenylalanine (Dopa) is a versatile molecule that enables marine mussels to achieve successful underwater adhesion. However, due to its complicated redox chemistry and vulnerability to oxidation, controlling surface adhesion and cohesion has been a challenging issue to overcome. Foot protein type 6 (fp-6), a thiol-rich interfacial mussel adhesive protein, has been reported as a proteinaceous antioxidant for mussels that helps Dopa maintain surface adhesion ability. In this study, we focused on the role of fp-6 in oxidized Dopa. The effect on the tautomer equilibrium of oxidized Dopa was investigated using recombinant fp-6 ( r fp-6) and Dopa-incorporated foot protein type 3 fast variant ( dr fp-3F), which were produced in bacterial cells. The redox chemistry of Dopa in dr fp-3F and the role of r fp-6 were observed using a UV-vis spectrophotometer and a surface forces apparatus (SFA). We discovered that r fp-6 shifts the tautomer equilibrium to ΔDopa as a preferred tautomer for oxidized Dopa in dr fp-3F and makes dr fp-3F better on underwater surface adhesion.