Ni Liwei, Kc Pawan, Mulvany Emily, Zhang Ge, Zhe Jiang
Department of Mechanical Engineering, University of Akron, Akron, OH, 44325, USA.
Department of Biomedical Engineering, University of Akron, Akron, OH, 44325, USA.
Biomed Microdevices. 2019 Feb 21;21(1):20. doi: 10.1007/s10544-019-0364-2.
We developed a device that can quickly apply versatile electrical stimulation (ES) signals to cells suspended in microfluidic channels and measure extracellular field potential simultaneously. The device could trap cells onto the surface of measurement electrodes for ES and push them to the downstream channel after ES by increasing pressure for continuous measurement. Cardiomyocytes, major functional cells in heart, together with human fibroblast cells and human umbilical vein endothelial cells, were tested with the device. Extracellular field potential signals generated from the cells were recorded. We found that under electrical stimulation, cardiomyocytes were triggered to alter their field potential, while non-excitable cells were not triggered. Hence this device can noninvasively distinguish electrically excitable cells from electrically non-excitable cells. Results have also shown that increased cardiomyocyte cell number led to increased magnitude and occurrence of the cell responses. This relationship could be used to detect the viable cells in a cardiac tissue. Application of variable ES signals on different cardiomyocyte clusters has shown that the application of ES clearly boosted cardiomyocytes electrical activities according to the stimulation frequency. In addition, we confirmed that the device can apply ES onto and detect the electrical responses from a mixed cell cluster; the responses from the mixed cluster is dependent on the ratio of cardiomyocytes. These results demonstrated that our device could be used as a tool to optimize ES conditions to facilitate the functional engineered cardiac tissue development.
我们开发了一种装置，该装置能够快速将多种电刺激（ES）信号施加到悬浮在微流控通道中的细胞上，并同时测量细胞外场电位。该装置可以将细胞捕获到测量电极表面以进行电刺激，并在电刺激后通过增加压力将细胞推向下游通道以进行连续测量。使用该装置对心脏中的主要功能细胞心肌细胞以及人成纤维细胞和人脐静脉内皮细胞进行了测试。记录了细胞产生的细胞外场电位信号。我们发现，在电刺激下，心肌细胞被触发改变其场电位，而非兴奋性细胞则未被触发。因此，该装置可以无创地区分电兴奋性细胞和电非兴奋性细胞。结果还表明，心肌细胞数量的增加导致细胞反应的幅度和发生率增加。这种关系可用于检测心脏组织中的活细胞。在不同心肌细胞簇上施加可变的电刺激信号表明，根据刺激频率，电刺激明显增强了心肌细胞的电活动。此外，我们证实该装置可以对混合细胞簇施加电刺激并检测其电反应；混合簇的反应取决于心肌细胞的比例。这些结果表明，我们的装置可以用作优化电刺激条件以促进功能性工程心脏组织发育的工具。
