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管中晶体管:通向三维生物电子学的途径。

Transistor in a tube: A route to three-dimensional bioelectronics.

机构信息

Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, UK.

Department of Bioelectronics, Ecole Nationale Supérieure des Mines, CMP-EMSE, Gardanne 13541, France.

出版信息

Sci Adv. 2018 Oct 26;4(10):eaat4253. doi: 10.1126/sciadv.aat4253. eCollection 2018 Oct.

Abstract

Advances in three-dimensional (3D) cell culture materials and techniques, which more accurately mimic in vivo systems to study biological phenomena, have fostered the development of organ and tissue models. While sophisticated 3D tissues can be generated, technology that can accurately assess the functionality of these complex models in a high-throughput and dynamic manner is not well adapted. Here, we present an organic bioelectronic device based on a conducting polymer scaffold integrated into an electrochemical transistor configuration. This platform supports the dual purpose of enabling 3D cell culture growth and real-time monitoring of the adhesion and growth of cells. We have adapted our system to a 3D tubular geometry facilitating free flow of nutrients, given its relevance in a variety of biological tissues (e.g., vascular, gastrointestinal, and kidney) and processes (e.g., blood flow). This biomimetic transistor in a tube does not require photolithography methods for preparation, allowing facile adaptation to the purpose. We demonstrate that epithelial and fibroblast cells grow readily and form tissue-like architectures within the conducting polymer scaffold that constitutes the channel of the transistor. The process of tissue formation inside the conducting polymer channel gradually modulates the transistor characteristics. Correlating the real-time changes in the steady-state characteristics of the transistor with the growth of the cultured tissue, we extract valuable insights regarding the transients of tissue formation. Our biomimetic platform enabling label-free, dynamic, and in situ measurements illustrates the potential for real-time monitoring of 3D cell culture and compatibility for use in long-term organ-on-chip platforms.

摘要

三维(3D)细胞培养材料和技术的进步,更准确地模拟体内系统以研究生物现象,促进了器官和组织模型的发展。虽然可以生成复杂的 3D 组织,但能够以高通量和动态方式准确评估这些复杂模型功能的技术还没有很好地适应。在这里,我们提出了一种基于导电聚合物支架集成到电化学晶体管配置中的有机生物电子设备。该平台支持 3D 细胞培养生长和实时监测细胞粘附和生长的双重目的。我们已经将我们的系统适应于 3D 管状几何形状,以促进营养物质的自由流动,因为它在各种生物组织(例如血管、胃肠道和肾脏)和过程(例如血流)中具有相关性。这种管状仿生晶体管不需要光刻方法进行制备,允许轻松适应目的。我们证明,上皮细胞和成纤维细胞在构成晶体管通道的导电聚合物支架内生长并形成组织样结构。在导电聚合物通道内形成组织的过程逐渐调节晶体管的特性。通过将晶体管的稳态特性的实时变化与培养组织的生长相关联,我们提取了有关组织形成瞬态的有价值的见解。我们的无标记、动态和原位测量仿生平台说明了实时监测 3D 细胞培养的潜力以及与长期器官芯片平台的兼容性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295a/6203411/b86a48462905/aat4253-F1.jpg

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