University of Applied Sciences Kaiserslautern, Informatics and Microsystem Technology, Amerikastr. 1, 66482 Zweibruecken, Germany.
Biosens Bioelectron. 2013 Feb 15;40(1):50-6. doi: 10.1016/j.bios.2012.06.006. Epub 2012 Jun 26.
In this study, impedance spectroscopy measurements of silicon-based open-gate field-effect transistor (FET) devices were utilized to study the adhesion status of cancer cells at a single cell level. We developed a trans-impedance amplifier circuit for the FETs with a higher bandwidth compared to a previously described system. The new system was characterized with a fast lock-in amplifier, which enabled measuring of impedance spectra up to 50 MHz. We studied cellular activities, including cell adhesion and anti-cancer drug induced apoptosis of human embryonic kidney (HEK293) and human lung adenocarcinoma epithelial (H441) cells. A well-known chemotherapeutic drug, topotecan hydrochloride, was used to investigate the effect of this drug to tumor cells cultured on the FET devices. The presence of the drug resulted in a 20% change in the amplitude of the impedance spectra at 200 kHz as a result of the induced apoptosis process. Real-time impedance measurements were performed inside an incubator at a constant frequency. The experimental results can be interpreted with an equivalent electronic circuit to resolve the influence of the system parameters. The developed method could be applied for the analysis of the specificity and efficacy of novel anti-cancer drugs in cancer therapy research on a single cell level in parallelized measurements.
在这项研究中，我们利用基于硅的开栅场效应晶体管（FET）器件的阻抗谱测量来研究单细胞水平的癌细胞黏附状态。我们为 FET 开发了一个跨阻放大器电路，与之前描述的系统相比，其带宽更高。新系统的特点是具有快速锁相放大器，能够测量高达 50 MHz 的阻抗谱。我们研究了细胞活动，包括人胚肾（HEK293）和人肺腺癌细胞上皮（H441）的细胞黏附和抗癌药物诱导的细胞凋亡。我们使用一种已知的化疗药物盐酸拓扑替康来研究该药物对在 FET 器件上培养的肿瘤细胞的影响。由于诱导的细胞凋亡过程，药物的存在导致在 200 kHz 时阻抗谱的幅度发生了 20%的变化。实时阻抗测量在孵育箱中以恒定频率进行。实验结果可以用等效电子电路进行解释，以解决系统参数的影响。该方法可用于分析新型抗癌药物在癌症治疗研究中的特异性和疗效，以及在平行测量中对单细胞水平的抗癌药物的分析。
