Faculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
Institute of Biomedical Engineering and Informatics, Technische Universität Ilmenau, 98693, Ilmenau, Germany.
Lab Chip. 2024 Aug 6;24(16):3945-3957. doi: 10.1039/d4lc00224e.
Electrical stimulation (ES) techniques, such as deep brain and transcranial electrical stimulation, have shown promise in alleviating the symptoms of depression and other neurological disorders . A new noninvasive ES method called temporal interference stimulation (TIS), possesses great potential as it can be used to steer the stimulation and possibly selectively modulate different brain regions. To study TIS in a controlled environment, we successfully established an 'TIS on a chip' setup using rat cortical neurons on microelectrode arrays (MEAs) in combination with a current stimulator. We validated the developed TIS system and demonstrated the spatial steerability of the stimulation by direct electric field measurements in the chip setup. We stimulated cultures of rat cortical neurons at 28 days (DIV) by two-channel stimulation delivering 1) TIS at 653 Hz and 643 Hz, resulting in a 10 Hz frequency envelope, 2) low-frequency stimulation (LFS) at 10 Hz and 3) high-frequency stimulation (HFS) at 653 Hz. Unstimulated cultures were used as control/sham. We observed the differences in the electric field strengths during TIS, HFS, and LFS. Moreover, HFS and LFS had the smallest effects on neuronal activity. Instead, TIS elicited neuronal electrophysiological responses, especially 24 hours after stimulation. Our 'TIS on a chip' approach eludicates the applicability of TIS as a method to modulate neuronal electrophysiological activity. The TIS on a chip approach provides spatially steerable stimuli while mitigating the effects of high stimulus fields near the stimulation electrodes. Thus, the approach opens new avenues for stimulation on a chip applications, allowing the study of neuronal responses to gain insights into the potential clinical applications of TIS in treating various brain disorders.
电刺激（ES）技术，如深部脑刺激和经颅电刺激，已显示出在缓解抑郁和其他神经障碍症状方面的潜力。一种新的非侵入性 ES 方法，称为时滞干扰刺激（TIS），具有很大的潜力，因为它可以用于引导刺激，并可能选择性地调节不同的脑区。为了在受控环境中研究 TIS，我们成功地使用微电极阵列（MEA）上的大鼠皮质神经元结合电流刺激器建立了一个“TIS 芯片”装置。我们验证了所开发的 TIS 系统，并通过在芯片装置中的直接电场测量证明了刺激的空间可控性。我们通过双通道刺激对 28 天（DIV）的大鼠皮质神经元培养物进行刺激，分别输送 1）653 Hz 和 643 Hz 的 TIS，产生 10 Hz 的频率包络，2）10 Hz 的低频刺激（LFS）和 3）653 Hz 的高频刺激（HFS）。未刺激的培养物用作对照/假刺激。我们观察了 TIS、HFS 和 LFS 期间电场强度的差异。此外，HFS 和 LFS 对神经元活动的影响最小。相反，TIS 诱发了神经元电生理反应，特别是在刺激后 24 小时。我们的“TIS 芯片”方法阐明了 TIS 作为一种调节神经元电生理活性的方法的适用性。TIS 芯片方法提供了空间可控的刺激，同时减轻了刺激电极附近的高刺激场的影响。因此，该方法为芯片上的刺激应用开辟了新的途径，允许研究神经元对 TIS 治疗各种脑障碍的潜在临床应用的反应。
