Smart Cell Culture Monitoring and Drug Test Platform Using CMOS Capacitive Sensor Array
Smart Cell Culture Monitoring and Drug Test Platform Using CMOS Capacitive Sensor Array
复制标题
DOI：
10.1109/tbme.2018.2866830
复制
发表时间：
2019-04-01
影响因子：
4.6
通讯作者：
Sawan, Mohamad
中科院分区：
文献类型：
--
作者：
Nabovati, Ghazal;Ghafar-Zadeh, Ebrahim;Sawan, Mohamad
提出了一种利用混合微流控CMOS平台监测药物细胞毒性的新方法。该平台由8 x 8电容传感器阵列组成，在同一芯片上集成了读出电路。在本文中，我们提出了一个逐层（LBL）的沉积技术，以涂层的表面微电极实现在最顶部的金属层在0.35 μ m的CMOS工艺。该过程成功地增强了传感微电极的生物相容性，从而在三天内提高了细胞活力。在此，我们展示并讨论了所提出的药物细胞毒性以及细胞生长监测平台的优势。该CMOS传感平台具有宽的输出动态范围，并允许在10至200 k Cells/ml的初始细胞浓度下跟踪细胞生长。我们还使用标准的Alamarblue基于细胞的测定和遗传霉素选择性抗生素（G418）作为对照和细胞毒性药物，分别引入非耐药H1299和耐药Hek 293细胞系。此外，提出了一种低复杂度的微流控封装技术，用于在CMOS芯片上创建和键合微孔，以进行快速测试和表征。由于具有进行无标记细胞分析的潜力，所提出的平台开辟了一条从传统到智能细胞分析技术的过渡途径，适用于各种生物应用，特别是高通量基于细胞的药物测试。
This paper presents a novel method for monitoring drug cytotoxicity using a hybrid microfluidic CMOS platform. This platform consists of an array of 8 x 8 capacitive sensors integrated with a readout circuit on the same chip. In this paper, we present a layer-by-layer (LBL) polyelectrolyte deposition technique to coat the surface of microelectrodes realized in the top most metal layer in 0.35-mu m CMOS process. This process successfully enhances the biocompatibility of sensing microelectrodes and consequently increases the cell viability over a three-day period. Herein, we demonstrate and discuss the advantage of the proposed platform for drug cytotoxicity as well as cellular growth monitoring. This CMOS sensing platform possesses a wide output dynamic range and allows tracking cell growth at initial cell concentrations ranging from 10 to 200 k Cells/ml. We also use a standard Alamarblue cell-based assay and Geneticin selective antibiotic (G418) as control and cytotoxic drugs introduced to non-resistant H1299 and resistant Hek293 cell lines, respectively. Furthermore, a low complexity microfluidic packaging technique is presented to create and bond micro-wells on CMOS chip for rapid test and characterization. With the potential to perform label-free cellular analysis, the proposed platform opens an avenue to transition from traditional to smart cellular analysis techniques suitable for a variety of biological applications, in particular high throughput cell-based drug testing.