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The human placenta is a critical organ, mediating the exchange of nutrients, oxygen, and waste products between fetus and mother. Placental malaria (PM) resulted from Plasmodium falciparum infections causes up to 200 thousand newborn deaths annually, mainly due to low birth weight, as well as 10 thousand mother deaths. In this work, a placenta-on-a-chip model is developed to mimic the nutrient exchange between the fetus and mother under the influence of PM. In this model, trophoblasts cells (facing infected or uninfected blood simulating maternal blood and termed "trophoblast side") and human umbilical vein endothelial cells (facing uninfected blood simulating fetal blood and termed "endothelial" side) are cultured on the opposite sides of an extracellular matrix gel in a compartmental microfluidic system, forming a physiological barrier between the co-flow tubular structure to mimic a simplified maternal-fetal interface in placental villi. The influences of infected erythrocytes (IEs) sequestration through cytoadhesion to chondroitin sulfate A (CSA) expressed on the surface of trophoblast cells, a critical feature of PM, on glucose transfer efficiency across the placental barrier was studied. To create glucose gradients across the barrier, uninfected erythrocyte or IE suspension with a higher glucose concentration was introduced into the "trophoblast side" and a culture medium with lower glucose concentration was introduced into the "endothelial side". The glucose levels in the endothelial channel in response to CSA-adherent erythrocytes infected with CS2 line of parasites in trophoblast channel under flow conditions was monitored. Uninfected erythrocytes served as a negative control. The results demonstrated that CSA-binding IEs added resistance to the simulated placental barrier for glucose perfusion and decreased the glucose transfer across this barrier. The results of this study can be used for better understanding of PM pathology and development of models useful in studying potential treatment of PM.

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RESUMEN

The human placenta plays a key role in reproduction and serves as a major interface for maternofetal exchange of nutrients. Study of human placenta pathology presents a great experimental challenge because it is not easily accessible. In this paper, a 3D placenta-on-a-chip model is developed by bioengineering techniques to simulate the placental interface between maternal and fetal blood in vitro. In this model, trophoblasts cells and human umbilical vein endothelial cells are cultured on the opposite sides of a porous polycarbonate membrane, which is sandwiched between two microfluidic channels. Glucose diffusion across this barrier is analyzed under shear flow conditions. Meanwhile, a numerical model of the 3D placenta-on-a-chip model is developed. Numerical results of concentration distributions and the convection-diffusion mass transport is compared to the results obtained from the experiments for validation. Finally, effects of flow rate and membrane porosity on glucose diffusion across the placental barrier are studied using the validated numerical model. The placental model developed here provides a potentially helpful tool to study a variety of other processes at the maternal-fetal interface, for example, effects of drugs or infections like malaria on transport of various substances across the placental barrier.

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Substantial growth in the biosensor research has enabled novel, sensitive and point-of-care diagnosis of human diseases in the last decade. This paper presents an overview of the research in the field of biosensors that can potentially predict and diagnosis of common placental pathologies. A survey of biomarkers in maternal circulation and their characterization methods is presented, including markers of oxidative stress, angiogenic factors, placental debris, and inflammatory biomarkers that are associated with various pathophysiological processes in the context of pregnancy complications. Novel biosensors enabled by microfluidics technology and nanomaterials is then reviewed. Representative designs of plasmonic and electrochemical biosensors for highly sensitive and multiplexed detection of biomarkers, as well as on-chip sample preparation and sensing for automatic biomarker detection are illustrated. New trends in organ-on-a-chip based placental disease models are highlighted to illustrate the capability of these in vitro disease models in better understanding the complex pathophysiological processes, including mass transfer across the placental barrier, oxidative stress, inflammation, and malaria infection. Biosensor technologies that can be potentially embedded in the placental models for real time, label-free monitoring of these processes and events are suggested. Merger of cell culture in microfluidics and biosensing can provide significant potential for new developments in advanced placental models, and tools for diagnosis, drug screening and efficacy testing.

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Aqueous two-phase system (ATPS) droplet generation has significant potential in biological and medical applications because of its excellent biocompatibility. However, the ultralow interfacial tension of ATPS makes droplet generation extremely challenging when compared with the conventional water-in-oil (W/O) system. In this paper, we passively produced ATPS droplets with a wide range of droplet size and high production rate without the involvement of an oil phase and external forces. For the first time, we reported important information of the flow rate and capillary (Ca) number for passive, oil-free ATPS droplet generation. It was found that the range of Ca numbers of the continuous phase under the jetting flow regime is 0.3-1.7, as compared to less than 0.1 in the W/O system, indicating the ultralow interfacial tension in ATPS. In addition, we successfully generated ATPS droplets with a radius as small as 7 µm at the maximum frequency up to 300 Hz, which has not been achieved in previous studies. The size and generation frequency of ATPS droplets can be controlled independently by adjusting the inlet pressures and corresponding flow rates. We found that the droplet size is correlated with the pressure and flow rate ratios with the power-law exponents of 0.8 and 0.2, respectively.