Stem cell‐derived cardiac spheroids are promising models for cardiac research and drug testing. However, generating contracting cardiac spheroids remains challenging because of the laborious experimental procedure. Here, we present a microfluidic hanging‐heart chip (HH‐chip) that uses a microchannel and flow‐driven system to facilitate cell loading and culture medium replacement operations to reduce the laborious manual handling involved in the generation of a large quantity of cardiac spheroids. The effectiveness of the HH‐chip was demonstrated by simultaneously forming 50 mouse embryonic stem cell‐derived embryonic bodies, which sequentially differentiated into 90% beating cardiac spheroids within 15 days of culture on the chip. A comparison of our HH‐chip method with traditional hanging‐drop and low‐attachment plate methods revealed that the HH‐chip could generate higher contracting proportions of cardiac spheroids with higher expression of cardiac markers. Additionally, we verified that the contraction frequencies of the cardiac spheroids generated from the HH‐chip were sensitive to cardiotoxic drugs. Overall, our results suggest that the microfluidic hanging drop chip‐based approach is a high‐throughput and highly efficient method for generating contracting mouse embryonic stem cell‐derived cardiac spheroids for cardiac toxicity and drug testing applications.

中文翻译：

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悬心芯片：一种便携式微流控装置，用于高通量生成收缩胚胎干细胞衍生的心脏球状体


干细胞来源的心脏球状体是心脏研究和药物测试的有前途的模型。然而，由于费力的实验过程，产生收缩的心脏球体仍然具有挑战性。在这里，我们提出了一种微流体吊心芯片 （HH-chip），它使用微通道和流动驱动系统来促进细胞加载和培养基更换操作，以减少产生大量心脏球体所涉及的费力手动操作。HH 芯片的有效性是通过同时形成 50 个小鼠胚胎干细胞衍生的胚胎体来证明的，这些胚胎体在芯片上培养后 15 天内依次分化为 90% 跳动的心脏球体。将我们的 HH 芯片方法与传统的悬滴和低连接板方法进行比较后发现，HH 芯片可以产生更高比例的心脏球状体收缩，心脏标志物表达更高。此外，我们验证了 HH 芯片产生的心脏球体的收缩频率对心脏毒性药物敏感。总体而言，我们的结果表明，基于微流体悬滴芯片的方法是一种高通量和高效的方法，用于生成用于心脏毒性和药物检测应用的收缩小鼠胚胎干细胞衍生的心脏球体。