An integrated microfluidic chip for studying the effects of neurotransmitters on neurospheroids
An integrated microfluidic chip for studying the effects of neurotransmitters on neurospheroids
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用于研究神经递质对神经球影响的集成微流控芯片
DOI：
10.1039/d2lc00755j
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发表时间：
2023
期刊：
影响因子：
6.1
通讯作者：
Que, Long
中科院分区：
文献类型：
--
作者：
Mao, Subin;Fonder, Catherine;Rubby, Md Fazlay;Phillips, Gregory J.;Sakaguchi, Donald S.;Que, Long
为了更好地了解中枢神经系统在健康和疾病中的功能，我们报道了一种集成芯片的开发，用于研究神经递质多巴胺和5-羟色胺对成年大鼠海马祖细胞(AHPC)神经球体的影响。这种芯片允许位于一个腔室中的多巴胺或5-羟色胺通过一系列故意错位的微柱形成的内置扩散屏障扩散到相邻腔室中培养的AHPC神经球体。微柱之间的空隙被多孔聚乙二醇凝胶填充，以调节扩散屏障的渗透性。在培养神经球体的小室内还集成了一个电化学传感器，从而可以监测多巴胺或5-羟色胺的浓度。实验表明，通过控制扩散屏障内的聚乙二醇凝胶的组成，神经球形室内的神经递质浓度可以在几个小时到10天以上的时间内增加。培养在芯片中的AHPC神经球体在多巴胺或5-羟色胺治疗后仍然高度存活。治疗后还观察到细胞增殖和神经元分化，表明AHPC神经球体是一种有价值的神经发生研究的体外脑模型。最后，我们证明，通过调节扩散屏障的渗透性，我们可以阻止大肠杆菌细胞通过扩散屏障的转移，同时允许多巴胺或5-羟色胺通过。这些结果表明，使用该芯片通过肠道-脑轴更好地了解微生物区系和大脑之间的相互作用是可行的。
To improve our understanding of how the central nervous system functions in health and disease, we report the development of an integrated chip for studying the effects of the neurotransmitters dopamine and serotonin on adult rat hippocampal progenitor cell (AHPC) neurospheroids. This chip allows dopamine or serotonin located in one chamber to diffuse to AHPC neurospheroids cultured in an adjacent chamber through a built-in diffusion barrier created by an array of intentionally misaligned micropillars. The gaps among the micropillars are filled with porous poly(ethylene glycol) (PEG) gel to tune the permeability of the diffusion barrier. An electrochemical sensor is also integrated within the chamber where the neurospheroids can be cultured, thereby allowing monitoring of the concentrations of dopamine or serotonin. Experiments show that concentrations of the neurotransmitters inside the neurospheroid chamber can be increased over a period of several hours to over 10 days by controlling the compositions of the PEG gel inside the diffusion barrier. The AHPC neurospheroids cultured in the chip remain highly viable following dopamine or serotonin treatment. Cell proliferation and neuronal differentiation have also been observed following treatment, revealing that the AHPC neurospheroids are a valuable in vitro brain model for neurogenesis research. Finally, we show that by tuning the permeability of diffusion barrier, we can block transfer of Escherichia coli cells across the diffusion barrier, while allowing dopamine or serotonin to pass through. These results suggest the feasibility of using the chip to better understand the interactions between microbiota and brain via the gut–brain axis.