The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

Coronavirus disease 2019 (COVID‐19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The models that can accurately resemble human‐relevant responses to viral infection are lacking. Here, a biomimetic human disease model on chip that allows to recapitulate lung injury and immune responses induced by SARS‐CoV‐2 in vitro at organ level is created. This human alveolar chip reproduce the key features of alveolar‐capillary barrier by coculture of human alveolar epithelium, microvascular endothelium, and circulating immune cells under fluidic flow in normal and disease. Upon SARS‐CoV‐2 infection, the epithelium exhibits higher susceptibility to virus than endothelium. Transcriptional analyses show activated innate immune responses in epithelium and cytokine‐dependent pathways in endothelium at day 3 post‐infection, revealing the distinctive responses in different cell types. Notably, viral infection causes the immune cell recruitment, endothelium detachment, and increased inflammatory cytokines release, suggesting the crucial role of immune cells involved in alveolar barrier injury and exacerbated inflammation. Treatment with remdesivir can inhibit viral replication and alleviate barrier disruption on chip. This organ chip model can closely mirror human‐relevant responses to SARS‐CoV‐2 infection, which is difficult to be achieved by in vitro models, providing a unique platform for COVID‐19 research and drug development.

Graphical abstract

A transportable optical clock refer to the 4s 2 S 1/2 -3d 2 D 5/2 electric quadrupole transition at 729 nm of single 40 Ca + trapped in mini Paul trap has been developed. The physical system of 40 Ca + optical clock is re-engineered from a bulky and complex setup to an integration of two subsystems: a compact single ion unit including ion trapping and detection modules, and a compact laser unit including laser sources, beam distributor and frequency reference modules. Apart from the electronics, the whole equipment has been constructed within a volume of 0.54 m 3 . The systematic fractional uncertainty has been evaluated to be 7.7×10 -17 , and the Allan deviation fits to be 14 2.3 10    by clock self-comparison with a probe pulse time 20 ms.

Prenatal exposure to environmental insults can increase the risk of developing neurodevelopmental disorders. Administration of the antiepileptic drug valproic acid (VPA) during pregnancy is tightly associated with a high risk of neurological disorders in offspring. However, the lack of an ideal human model hinders our comprehensive understanding of the impact of VPA exposure on fetal brain development, especially in early gestation. Herein, we present the first report indicating the effects of VPA on brain development at early stages using engineered cortical organoids from human induced pluripotent stem cells (hiPSCs). Cortical organoids were generated on micropillar arrays in a controlled manner, recapitulating the critical features of human brain development during early gestation. With VPA exposure, cortical organoids exhibited neurodevelopmental dysfunction characterized by increased neuron progenitors, inhibited neuronal differentiation and altered forebrain regionalization. Transcriptome analysis showed new markedly altered genes (e.g., KLHL1, LHX9, and MGARP) and a large number of differential expression genes (DEGs), some of which are related to autism. In particular, comparison of transcriptome data via GSEA and correlation analysis revealed the high similarity between VPA-exposed organoids with the postmortem ASD brain and autism patient-derived organoids, implying the high risk of autism with prenatal VPA exposure, even in early gestation. These new findings facilitate a better understanding of the cellular and molecular mechanisms underlying postnatal brain disorders (such as autism) with prenatal VPA exposure. This established cortical organoid-on-a-chip platform is valuable for probing neurodevelopmental disorders under environmental exposure and can be extended to applications in the study of diseases and drug testing.

The cell encapsulation technology is promising for generation of functional carriers with well-tailored structures for efficient transplantation and immunoprotection of cells/tissues. Stem cell organoids are highly potential for recapitulating the intricate architectures and functionalities of native organs and also providing an unlimited cell source for cellular replacement therapy. However, it remains challenging for loading the organoids with hundreds of micrometers size by current existing cell carriers. Herein, a simple and facile coextrusion strategy is developed for controllable fabrication of Ca-alginate/poly(ethylene imine) (Alg/ PEI) macrocapsules for efficient encapsulation and cultivation of organoids. Human-induced pluripotent stem cell (hiPSC)-derived islet organoids are encapsulated in the aqueous compartments of the capsules and immunoisolated by a semipermeable Alg/PEI shell. Via electrostatic interactions, a PEI polyelectrolyte can be incorporated in the shell for restricting its swelling, thus effectively improving the stability of the capsules. The Alg/PEI macrocapsules are featured with desirable selective permeability for immunoisolation of antibodies from reaching the loaded organoids. Meanwhile, they also exhibit excellent permeability for mass transfer due to their well-defined core−shell structure. As such, the encapsulated islet organoids contain islet-specific multicellular components, with high viability and sensitive glucosestimulated insulin secretion function. The proposed approach provides a versatile encapsulation system for tissue engineering and regenerative medicine applications.

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