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从实验室芯片到即时护理活细胞装置:一种用于现场细胞培养和高通量药物筛选的微流控装置的开发。

From Chips-in-Lab to Point-of-Care Live Cell Device: Development of a Microfluidic Device for On-Site Cell Culture and High-Throughput Drug Screening.

作者信息

Feng Yibo, Che Bingchen, Fu Jiahao, Sun Yu, Ma Wenju, Tian Jing, Dai Liang, Jing Guangyin, Zhao Wei, Sun Dan, Zhang Ce

机构信息

State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, No. 1, Xuefu Avenue, Xi'an 710127, Shaanxi, China.

School of Physics, Northwest University, No. 1 Xuefu Avenue, Xi'an 710127, Shaanxi, China.

出版信息

ACS Biomater Sci Eng. 2024 Aug 12;10(8):5399-5408. doi: 10.1021/acsbiomaterials.4c00766. Epub 2024 Jul 20.

Abstract

Live cell assays provide real-time data of cellular responses. In combination with microfluidics, applications such as automated and high-throughput drug screening on live cells can be accomplished in small devices. However, their application in point-of-care testing (POCT) is limited by the requirement for bulky equipment to maintain optimal cell culture conditions. In this study, we propose a POCT device that allows on-site cell culture and high-throughput drug screening on live cells. We first observe that cell viabilities are substantially affected by liquid evaporation within the microfluidic device, which is intrinsic to the polydimethylsiloxane (PDMS) material due to its hydrophobic nature and nanopatterned surface. The unwanted PDMS-liquid-air interface in the cell culture environment can be eliminated by maintaining a persistent humidity of 95-100% or submerging the whole microfluidic device under water. Our results demonstrate that in the POCT device equipped with a water tank, both primary cells and cell lines can be maintained for up to 1 week without the need for external cell culture equipment. Moreover, this device is powered by a standard alkali battery and can automatically screen over 5000 combinatorial drug conditions for regulating neural stem cell differentiation. By monitoring dynamic variations in fluorescent markers, we determine the optimal doses of platelet-derived growth factor and epidermal growth factor to suppress proinflammatory S100A9-induced neuronal toxicities. Overall, this study presents an opportunity to transform lab-on-a-chip technology from a laboratory-based approach to actual point-of-care devices capable of performing complex experimental procedures on-site and offers significant advancements in the fields of personalized medicine and rapid clinical diagnostics.

摘要

活细胞分析可提供细胞反应的实时数据。与微流体技术相结合,可在小型设备中实现诸如对活细胞进行自动化高通量药物筛选等应用。然而,它们在即时检验(POCT)中的应用受到维持最佳细胞培养条件所需的大型设备的限制。在本研究中,我们提出了一种POCT设备,可对活细胞进行现场细胞培养和高通量药物筛选。我们首先观察到,微流控设备内的液体蒸发会显著影响细胞活力,由于聚二甲基硅氧烷(PDMS)材料的疏水性和纳米图案化表面,这种现象在该材料中是固有的。通过保持95 - 100%的持续湿度或将整个微流控设备浸没在水中,可以消除细胞培养环境中不需要的PDMS - 液体 - 空气界面。我们的结果表明,在配备水箱的POCT设备中,原代细胞和细胞系均可维持长达1周,无需外部细胞培养设备。此外,该设备由标准碱性电池供电,可自动筛选超过5000种组合药物条件以调节神经干细胞分化。通过监测荧光标记物的动态变化,我们确定了血小板衍生生长因子和表皮生长因子的最佳剂量,以抑制促炎S100A9诱导的神经元毒性。总体而言,本研究提供了一个机会,将芯片实验室技术从基于实验室的方法转变为能够在现场执行复杂实验程序的实际即时检验设备,并在个性化医学和快速临床诊断领域取得了重大进展。

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