Highlights  Cell spheroids are spherical aggregates best mimicking the tissue microenvironment.  Spheroid culture better recapitulates the in-vivo condition in microfluidic chips.  Microfluidics provides rapid spheroid formation with size uniformity and control.  These chips contain microwells, microstructures, droplet generators, etc.  To fabricate such chips, some design considerations must be taken into account.

Aminolysis of a variety of epoxides by aliphatic and aromatic amines in water, in the absence of any catalyst with high yields, is reported. Beta-amino alcohols were formed under mild conditions with high selectivity and in excellent yields. [reaction: see text]

Highly efficient one-pot reactions of amines and carbon disulfide with alpha,beta-unsaturated compounds were carried out in water under a mild and green procedure with high yields.

Microfluidic devices have been widely used for biological and cellular studies. Microbioreactors for three-dimensional (3D) multicellular spheroid culture are now considered as the next generation in in vitro diagnostic tools. The feasibility of using 3D cell aggregates to form multicellular spheroids in a microbioreactor with U-shaped barriers has been demonstrated experimentally. A barrier array is an alternative to commonly used microwell traps. The present study investigates oxygen and glucose concentration distributions as key parameters in a U-shaped array microbioreactor using finite element simulation. The effect of spheroid diameter, inlet concentration and flow rate of the medium are systematically studied. In all cases, the channel walls are considered to be permeable to oxygen. Necrotic and hypoxic or quiescent regions corresponding to both oxygen and glucose concentration distributions are identified for various conditions. The results show that the entire quiescent and necrotic regions become larger with increasing spheroid diameter and decreasing inlet and wall concentration. The shear stress (0.5–9 mPa) imposed on the spheroid surface by the fluid flow was compared with the critical values to predict possible damage to the cells. Finally, optimum range of medium inlet concentration (0.13–0.2 mM for oxygen and 3–11 mM for glucose) and flow rate (5–20 μL/min) are found to form the largest possible multicellular spheroid (500 μm), without any quiescent and necrotic regions with an acceptable shear stress. The effect of cell-trap types on the oxygen and glucose concentration inside the spheroid was also investigated. The levels of oxygen and glucose concentration for the microwell are much lower than those for the other two traps. The U-shaped barrier created with microposts allows for a continuous flow of culture medium, and so improves the glucose concentration compared to that in the integrated U-shaped barrier. Oxygen concentration for both types of U-shaped barriers is nearly the same. Due to the advantage of using U-shaped barriers to culture multicellular spheroids, the results of this paper can help to choose the experimental and design parameters of the microbioreactor.

BackgroundDementia due to Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the two most common neurodegenerative causes of dementia. They commonly occur together, especially in older people, but clinical identification of these diseases in dementia is difficult in such circumstances. We therefore conducted a study using cases with both comprehensive prospective clinical assessments and complete neuropathological examination to determine if it is possible to identify such mixed cases clinically and to determine features which may identify DLB in the presence of AD dementia.MethodsAt Newcastle Brain Bank we identified subjects who had a clinical diagnosis of dementia and who also had autopsy diagnoses of pure AD, pure DLB, or mixed AD+DLB. All subjects had undergone prospective longitudinal clinical assessments. Mixed AD+DLB patients met neuropathological criteria for both DLB (limbic/neocortical Lewy body disease) and AD (Braak stage V/VI and CERAD B/C). The records of these subjects were carefully reviewed by two specialists in old-age psychiatry blind to autopsy findings to determine baseline and final clinical diagnoses based on these detailed records. The presence of characteristic Lewy body symptoms and other clinical information was also recorded.ResultsOf 59 subjects included, 19 were AD, 18 DLB, and 22 mixed AD+DLB. At baseline no subjects were correctly identified as having mixed AD+DLB and by final diagnosis only 23% were identified. The only symptom which helped in identifying the presence of Lewy body disease in the context of a mixed AD+DLB dementia was complex visual hallucinations.ConclusionsWhilst the identification of DLB in the context of a dementia with an AD pattern is difficult, the emergence of complex visual hallucinations in the context of such a degenerative dementia suggests the presence of Lewy body disease and should encourage a careful assessment. Biomarkers appear likely to be necessary to help improve identification of different disease subtypes underlying dementia.