Heer F, Hafizovic S, Ugniwenko T, Frey U, Franks W, Perriard E, Perriard J-C, Blau A, Ziegler C, Hierlemann A
Physical Electronics Laboratory, ETH Zürich, ETH Hönggerberg, HPT H 4.2, Wolfgang-Pauli-Strasse 16, CH-8093 Zurich, Switzerland.
Biosens Bioelectron. 2007 May 15;22(11):2546-53. doi: 10.1016/j.bios.2006.10.003. Epub 2006 Nov 13.
A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.
高度的连通性以及神经细胞或神经网络的协同电活动被认为是大脑能够进行高度复杂信息处理的原因。同样，动物心脏的效能在很大程度上取决于这种细胞的协同活动。为了增进我们对这些复杂生物系统的理解，需要高时空分辨率技术来监测细胞电活动以及细胞与记录设备之间理想的无缝交互。在此，我们展示一种采用互补金属氧化物半导体（CMOS）技术的单片微系统，该系统在标准电子技术与培养的电生细胞之间提供双向通信（刺激和记录）。该微芯片可直接用作细胞培养的基质，其每个电极都设有用于刺激和即时细胞信号处理的电路单元，并且提供片上信号转换以及数字接口，从而能够以卓越的信号质量实现非常快速、几乎实时的交互（从事件识别到例如特定刺激的循环时间为2毫秒）。将展示使用神经元和心脏细胞培养物进行的相应自发和刺激电活动记录。该系统可用于例如研究神经网络的发育、揭示神经元可塑性的影响以及研究细胞或网络对药物治疗的反应。
