中国科学院动物研究所的赵方庆团队发现，定制的微流控芯片设计实现具有广视野的低成本三维时空转录组学研究。2024年9月10日，《自然—遗传学》杂志在线发表了这项成果。

研究人员介绍了用于空间转录组测序的微流控辅助网格芯片（MAGIC-seq），这是一种结合了碳二亚胺化学、空间组合索引和创新微流控设计的新方法。该技术能够对多种组织类型进行敏感且可重复的分析，实现通量提高八倍，成本极低，并减少了批次效应。

MAGIC-seq通过提高条形码标记效率，突破了传统微流控的限制，能够分析完整的新生小鼠切片，以接近单细胞分辨率提供全面的细胞结构解析，揭示转录变化和小鼠器官发生的动态轨迹。

研究人员由93个切片组成的小鼠大脑发育过程的三维转录组图谱展示了分子和细胞的景观，为神经科学和发育生物学提供了宝贵的资源。总体而言，MAGIC-seq是一种高通量、低成本、广视野且多功能的空间转录组研究方法。

据介绍，空间转录组技术为复杂组织的分子组织提供了前所未有的洞察。然而，如何结合成本效益、高通量、广视野和对三维体积的兼容性一直是一个挑战。

附：英文原文

Title: Custom microfluidic chip design enables cost-effective three-dimensional spatiotemporal transcriptomics with a wide field of view

Author: Zhu, Junjie, Pang, Kun, Hu, Beiyu, He, Ruiqiao, Wang, Ning, Jiang, Zewen, Ji, Peifeng, Zhao, Fangqing

Issue&Volume: 2024-09-10

Abstract: Spatial transcriptomic techniques offer unprecedented insights into the molecular organization of complex tissues. However, integrating cost-effectiveness, high throughput, a wide field of view and compatibility with three-dimensional (3D) volumes has been challenging. Here we introduce microfluidics-assisted grid chips for spatial transcriptome sequencing (MAGIC-seq), a new method that combines carbodiimide chemistry, spatial combinatorial indexing and innovative microfluidics design. This technique allows sensitive and reproducible profiling of diverse tissue types, achieving an eightfold increase in throughput, minimal cost and reduced batch effects. MAGIC-seq breaks conventional microfluidics limits by enhancing barcoding efficiency and enables analysis of whole postnatal mouse sections, providing comprehensive cellular structure elucidation at near single-cell resolution, uncovering transcriptional variations and dynamic trajectories of mouse organogenesis. Our 3D transcriptomic atlas of the developing mouse brain, consisting of 93 sections, reveals the molecular and cellular landscape, serving as a valuable resource for neuroscience and developmental biology. Overall, MAGIC-seq is a high-throughput, cost-effective, large field of view and versatile method for spatial transcriptomic studies.

DOI: 10.1038/s41588-024-01906-4

Source: https://www.nature.com/articles/s41588-024-01906-4