Istituto Italiano di Tecnologia, 16163 Genova, Italy.
Lab Chip. 2018 Nov 6;18(22):3492-3500. doi: 10.1039/c8lc00435h.
Biological studies on in vitro cell cultures are of fundamental importance to investigate cell response to external stimuli, such as new drugs for the treatment of specific pathologies, or to study communication between electrogenic cells. Although three-dimensional (3D) nanostructures brought tremendous improvements on biosensors used for various biological in vitro studies, including drug delivery and electrical recording, there is still a lack of multifunctional capabilities that could help gain deeper insights in several bio-related research fields. In this work, the electrical recording of large cell ensembles and the intracellular delivery of few selected cells are combined on the same device by integrating microfluidic channels on the bottom of a multi-electrode array decorated with 3D hollow nanostructures. The novel platform allows the recording of intracellular-like action potentials from large ensembles of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) and from the HL-1 line, while different molecules are selectively delivered into single/few targeted cells. The proposed approach shows high potential for enabling new comprehensive studies that can relate drug effects to network level cell communication processes.
体外细胞培养的生物学研究对于研究细胞对外界刺激的反应非常重要,例如治疗特定病理的新药,或研究电活性细胞之间的通信。尽管三维(3D)纳米结构在用于各种体外生物学研究的生物传感器方面带来了巨大的改进,包括药物输送和电记录,但仍缺乏多功能性,这可能有助于深入了解几个与生物相关的研究领域。在这项工作中,通过在多电极阵列的底部集成微流道,将电记录大细胞群体和对少数选定细胞进行细胞内递药这两种功能整合在同一个装置上,该多电极阵列由 3D 中空纳米结构装饰而成。该新型平台允许记录源自人诱导多能干细胞(hiPSC)和 HL-1 系的大型心肌细胞群体的类似于细胞内的动作电位,同时可将不同的分子选择性递送至单个/少数靶向细胞。该方法具有很高的潜力,可以进行新的综合研究,将药物作用与网络级细胞通信过程联系起来。