纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Research and development of liquid hydrogen (LH2) temperature monitoring system for marine applications

Monitoring the temperature in liquid hydrogen (LH₂) storage tanks on ships is important for the safety of maritime navigation. In addition, accurate temperature measurement is also required for commercial transactions. Temperature and pressure define the density of liquid hydrogen, which is directly linked to trading interests. In this study, we developed and tested a liquid hydrogen temperature monitoring system that uses platinum resistance sensors with a nominal electrical resistance of approximately 1000 Ω at room temperature, PT-1000, for marine applications. The temperature measurements were carried out using a newly developed temperature monitoring system under different pressure conditions. The measured values are compared with a calibrated reference PT-1000 resistance thermometer. We confirm a measurement accuracy of ±50 mK in a pressure range of 0.1 MPa–0.5 MPa.     

Evaluation of hydrodynamic behavior of the perforated gas distributor of industrial gas phase polymerization reactor using CFD-PBM coupled model

A 2D computational fluid dynamics (Eulerian–Eulerian) multiphase flow model coupled with a population balance model (CFD-PBM) was implemented to investigate the fluidization structure in terms of entrance region in an industrial-scale gas phase fluidized bed reactor. The simulation results were compared with the industrial data, and good agreement was observed. Two cases including perforated distributor and complete sparger were applied to examine the flow structure through the bed. The parametric sensitivity analysis of time step, number of node, drag coefficient, and specularity coefficient was carried out. It was found that the results were more sensitive to the drag model. The results showed that the entrance configuration has significant effect on the flow structure. While the dead zones are created in both corners of the distributors, the perforated distributor generates more startup bubbles, heterogeneous flow field, and better gas–solid interaction above the entrance region due to jet formation.     

Upscaled DEM-CFD model for vibrated fluidized bed based on particle-scale similarities

Simulation based on discrete element method (DEM) coupled with computational fluid dynamics (CFD), coupled DEM-CFD, is a powerful tool for investigating the details of dense particle–fluid interaction problems such as in fluidized beds and pneumatic conveyers. The addition of a mechanical vibration to a system can drastically alter the particle and fluid flows; however, their detailed mechanisms are not well understood. In this study, a DEM-CFD model based on a non-inertial frame of reference is developed to achieve a better understanding of the influence of vibration in a vibrated fluidized bed. Because the high computational cost of DEM-CFD calculations is still a major problem, an upscaled coarse-graining model is also employed. To realize similar behaviors with enlarged model particles, non-dimensional parameters at the particle scale were deduced from the governing equations. The suitability and limitations of the proposed model were examined for a density segregation problem of a binary system. To reduce the computational costs, we show that the ratio between the bed width and model particle size can be reduced to a minimum value of 100; to obtain similar segregation behaviors, the ratio between the bed height and model particle size is considered unchanged.     

旋流分离-颗粒床耦合气固分离装备旋流场静压分布

针对一种集旋风分离器和内置颗粒床优势于一体的新型耦合气固分离装备在无灰负荷及固定床操作条件入口环形空间、分离空间和灰斗内静压场进行研究。结果表明，静压沿周向为非对称分布，轴向为非均匀分布，径向则呈中心低两侧高分布；且存在着静压分布的降压区(0?~180?，以入口处为0?)和增压区(180?~360?)；装备中心的负压及旋流作用在轴向高度H=6.41D(D为旋风壳体内径)以下对静压的影响不再显著；内置颗粒床外壁附近存在“滞留层”，有利于提高装备的分离性能。根据实验数据给出了静压周向分布和静压轴向分布的经验公式。     

Studying local liquid velocity in liquid–solid packed bed using the newly developed X-ray DIR technique

Combination of X-ray Digital Industrial Radiography (DIR) and Particle Tracking Velocimetry (PTV) techniques for local liquid velocity measurement (V_LL) has been newly developed and successfully applied for trickle bed reactor (TBR). The technique was validated against newly developed fiber optical probe technique. This work attempts to highlight the applicability of this newly developed technique on a liquid–solid packed bed reactor. In this work, liquid was represented by water and solids were represented by EPS beads. The EPS beads were chosen because of its low density property. Three superficial liquid velocities (V_SL) were applied to the system. The experiment was replicated four times. The digital industrial radiography (DIR) consists of a complementary metal oxide semiconductor (CMOS) digital detector and X-ray source. Results of this work suggest that the technique has been successfully applied and comparable with previous work that has been done in the literature. It also suggests that there will be a maximum measurable interstitial liquid velocity when it travel inside the packed bed. The measured V_LL can have a maximum range that is between 4 and 4.7 times that of its V_SL. For V_SL=0.42±±2%, the V_LL-Max is in between 1.7 cm/s and 1.9 cm/s, V_SL=0.84±±2%, the V_LL-Max is in between 3.6 cm/s and 4.0 cm/s, and for V_SL=1.11±±2%, the V_LL-Max is in between 4.3 cm/s and 4.8 cm/s.     

Additive manufacturing of bipolar plates for hydrogen production in proton exchange membrane water electrolysis cells

Water electrolysis is a process that can produce hydrogen in a clean way when renewable energy sources are used. This allows managing large renewable surpluses and transferring this energy to other sectors, such as industry or transport. Among the electrolytic technologies to produce hydrogen, proton exchange membrane (PEM) electrolysis is a promising alternative. One of the main components of PEM electrolysis cells are the bipolar plates, which are machined with a series of flow distribution channels, largely responsible for their performance and durability. In this work, AISI 316L stainless steel bipolar plates have been built by additive manufacturing (AM), using laser powder bed fusion (PBF-L) technology. These bipolar plates were subjected to ex-situ corrosion tests and assembled in an electrolysis cell to evaluate the polarization curve. Furthermore, the obtained results were compared with bipolar plates manufactured by conventional machining processes (MEC). The obtained experimental results are very similar for both manufacturing methods. This demonstrates the viability of the PBF-L technology to produce metal bipolar plates for PEM electrolyzers and opens the possibilities to design new and more complex flow distribution channels and to test these designs in initial phases before scaling them to larger surfaces.     

油页岩矿物质催化半焦燃烧特性及机理

利用微型流化床反应分析仪（MFBRA）研究了油页岩矿物质催化半焦燃烧特性，重点考察了半焦内部矿物质和外部页岩灰床料对半焦燃烧的催化作用，揭示了流化床反应器中半焦燃烧过程和机理。结果表明：内部矿物质和外部床料对半焦燃烧均具有明显催化作用，而两者共同催化效果最为显著。矿物质中CaO和Fe₂O₃对半焦燃烧具有催化活性，CaO催化作用强于Fe₂O₃。油页岩半焦燃烧反应活化能在60.41~78.97 kJ/mol之间，矿物质的催化作用会明显降低反应活化能。流化床反应器中，矿物质对半焦燃烧的催化作用主要表现在四个反应，即：挥发分裂解和燃烧、半焦表面炭燃烧、半焦内部炭燃烧以及一氧化碳燃烧。     

Development and monitoring of an integrated bioprocess for production of a potential malaria vaccine with Pichia pastoris

An engineered variant of the yeast Pichia pastoris was used to produce the potential malaria vaccine D1M1. This paper describes the implementation of an expanded bed adsorption chromatography step into a sequential cultivation process of the yeast in order to link protein expression, cell release, and product capture of the secreted protein in a fully automated plant. The process is operated with a semi-continuous strategy for an integrated production. Process improvements have been achieved using design of experiments. Resulting purities of product achieved up to 87% with recoveries of 51% in a single downstream operation. Furthermore, a multivariate analysis of historical batch data was used to develop a golden batch model for process monitoring.