Controlled cell assembly is essential for fabricating in vitro 3D models that mimic the physiology of in vivo cellular architectures. Whereas tissue engineering techniques often rely on intrusive magnetic nanoparticles placed in cells and hydrogel encapsulation of cells to produce multilayered cellular constructs, we describe a high-throughput, label-free, and scaffold-free magnetic field-guided technique that assembles cells into a layered aggregate. An inhomogeneous magnetic field influences the diamagnetic cells suspended in a paramagnetic culture medium. Driven by the magnetic susceptibility difference and the field gradient, the cells are displaced toward the region of lowest field strength. Two cell lines are used to demonstrate the sequential assembly of layer-on-layer aggregates in microwells within 6 h. The effect of magnet size on the assembly dynamics is characterized and a microwell size criterion for the highest cell aggregation provided. Label-free magnetic-field-assisted assembly is relevant for on-demand scalable biofabrication of complex layered structures. Potential applications include drug discovery, developmental biology, lab-on-chip devices, and cancer research.

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无标签磁场辅助的层到层细胞结构组装

控制细胞的组装对于制造模仿体内细胞结构生理的体外3D模型至关重要。尽管组织工程技术通常依赖于放置在细胞中的侵入性磁性纳米颗粒和细胞的水凝胶封装来产生多层细胞构建体，但我们描述了一种高通量，无标记和无支架的磁场引导技术，该技术将细胞组装成分层骨料。不均匀的磁场影响悬浮在顺磁性培养基中的反磁性细胞。在磁化率差和场梯度的驱动下，细胞向最低场强区域移动。使用两个细胞系来证明在6小时内微孔中逐层聚集体的顺序组装。表征了磁体尺寸对组装动力学的影响，并提供了用于最高细胞聚集的微孔尺寸标准。无标签磁场辅助组件与复杂分层结构的按需可扩展生物制造有关。潜在的应用包括药物发现，发育生物学，芯片实验室设备和癌症研究。