Xi Biao, Yu Naichen, Wang Xiaobo, Xu Xiao, Abassi Yama A
ACEA Biosciences, San Diego, CA 92121, USA.
Biotechnol J. 2008 Apr;3(4):484-95. doi: 10.1002/biot.200800020.
Cell-based assays are an important part of the drug discovery process allowing for interrogation of targets and pathways in a more physiological setting compared to biochemical assays. One of the main hurdles in the cell-based assay field is to design sufficiently robust assays with adequate signal to noise parameters while maintaining the inherent physiology of the pathway or target being investigated. Conventional label and reporter-based cell assays may be more prone to artifacts due to considerable manipulation of the cell either by the label or over-expression of targets or reporter proteins. Cell-based label-free technologies preclude the need for cellular labeling or over-expression of reporter proteins, utilizing the inherent morphological and adhesive characteristics of the cell as a physiologically relevant and quantitative readout for various cellular assays. Furthermore, these technologies utilize non-invasive measurements allowing for time resolution and kinetics in the assay. In this article, we have reviewed the various label-free technologies that are being used in drug discovery settings and have focused our discussion on impedance-based label-free technologies and its main applications in drug discovery.
基于细胞的检测是药物发现过程的重要组成部分,与生化检测相比,它能够在更接近生理的环境中对靶点和信号通路进行研究。基于细胞的检测领域的主要障碍之一是设计出足够稳健的检测方法,使其具有适当的信噪比参数,同时保持所研究信号通路或靶点的固有生理特性。传统的基于标记和报告基因的细胞检测可能更容易产生假象,因为细胞会受到标记、靶点或报告蛋白的过表达等大量操作的影响。基于细胞的无标记技术无需对细胞进行标记或报告蛋白的过表达,而是利用细胞固有的形态和黏附特性,作为各种细胞检测的生理相关且定量的读数。此外,这些技术采用非侵入性测量方法,可实现检测中的时间分辨和动力学分析。在本文中,我们综述了药物发现中正在使用的各种无标记技术,并将讨论重点放在基于阻抗的无标记技术及其在药物发现中的主要应用上。