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清华大学学报(自然科学版)  2016, Vol. 56 Issue (7): 751-758    DOI: 10.16511/j.cnki.qhdxxb.2016.21.040
  生物与生物医学 本期目录 | 过刊浏览 | 高级检索 |
基于电阻抗多模式检测芯片的体外热疗
谢新武1,2, 刘蔚然1, 刘冉1
1. 清华大学 医学院, 生物医学工程系, 北京 10084;
2. 军事医学科学院 卫生装备研究所, 天津 300161
In vitro hyperthermia based on a multi-mode detection chip with impedance sensing
XIE Xinwu1,2, LIU Weiran1, LIU Ran1
1. Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China;
2. Institute of Medical Equipment, China Academy of Military Medical Sciences, Tianjin, 300161, China
全文: PDF(4990 KB)  
输出: BibTeX | EndNote (RIS)      
摘要 热疗是继手术、化疗、放疗之后对癌症的一大治疗手段,但是目前其机理尚不明确,体外研究结论与临床应用尚有差距。为更好地研究在热应激/热疗过程中的细胞变化,该文构建了一套集成细胞电阻抗非标记动态检测、细胞形态动态记录、荧光标记检测功能并且能够自动测控温度的微全分析系统,对其控温性能进行了仿真与实测检验,对细胞培养及增殖过程进行了非标记连续监测,并利用此实验系统进行了癌细胞在2种热疗条件下的动态多模式检测。实验结果表明:HeLa细胞在41℃,2 h热疗作用下,阻抗呈现“V”型变化,形态快速收缩后又迅速恢复贴壁,荧光标记检测显示细胞活力无明显改变;而在2次55℃,2 min脉冲式热疗作用下,细胞阻抗呈现“L”型变化,细胞杀伤效果明显。该系统将传统标记技术与非标记检测技术结合,可用于细胞热应激/热疗的相关研究。
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谢新武
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刘冉
关键词 细胞-基质电阻抗测量热疗芯片实验室多模式检测    
Abstract:Hyperthermia is a useful method for cancer treatment after surgery, chemotherapy and radiotherapy for numerous types of cancers. However, the mechanism is not yet fully understood and some in vitro results cannot be repeated in clinical applications; thus, further research is needed. In this study, a lab-on-a-chip device and a corresponding detection system was constructed to study in vitro hyperthermia. The device incorporated electric cell-substrate impedance sensing (ECIS), morphological imaging, and fluorescence observation during and after cells were thermally treated in situ with automatic on-chip temperature control. The temperature control was tested in an incubator. The cell culture and impedance sensing were also validated. Then, cancer cells were treated and monitored by the system for two hyperthermia conditions. The impedance curve with rectangle hyperthermia control of 41℃ for 2 h shows a "V" shape change during the 41℃ treatment with the cells quickly shrinking and re-adhering without any obvious viability changes in the fluorescent labeling images. However, two hyperthermia pulses at 55℃ for 2 min caused cell impedance "L" shape changes and killed most of the cells. These results demonstrate that this device with un-labeled and labeled methods is a useful tool for in vitro research on thermal therapy.
Key wordselectric cell-substrate impedance sensing (ECIS)    hyperthermia    lab on a chip    multi-mode detections
收稿日期: 2015-05-03      出版日期: 2016-07-22
ZTFLH:  O652.7  
基金资助:国家重大科学仪器设备开发专项(2011YQ030134)
通讯作者: 刘冉,助理研究员。E-mail:liuran@tsinghua.edu.cn     E-mail: liuran@tsinghua.edu.cn
引用本文:   
谢新武, 刘蔚然, 刘冉. 基于电阻抗多模式检测芯片的体外热疗[J]. 清华大学学报(自然科学版), 2016, 56(7): 751-758.
XIE Xinwu, LIU Weiran, LIU Ran. In vitro hyperthermia based on a multi-mode detection chip with impedance sensing. Journal of Tsinghua University(Science and Technology), 2016, 56(7): 751-758.
链接本文:  
http://jst.tsinghuajournals.com/CN/10.16511/j.cnki.qhdxxb.2016.21.040  或          http://jst.tsinghuajournals.com/CN/Y2016/V56/I7/751
  图1 实验平台位于培养箱内的部分
  图2 芯片构成
  图3 叉指电极单元
  图4 显微镜明场,绿色荧光和红色荧光照片
  图5 芯片温度场仿真结果
  图6 芯片温度控制效果
  图7 培养箱内37℃培养条件下细胞贴壁生长、增殖的电阻抗曲线
  图8 GFPGHeLa细胞41℃热疗的温度、阻抗曲线以及细胞形态与荧光照片对比
  图9 GFPGHeLa细胞55℃脉冲式热疗的温度、阻抗曲线以及细胞形态与荧光照片对比
[1] Coffey D S, Getzenberg R H, DeWeese T L. Hyperthermic biology and cancer therapies:A hypothesis for the "Lance Armstrong effect"[J]. JAMA, 2006, 296(4):445-448.
[2] Jones E L, Oleson J R, Prosnitz L R, et al. Randomized trial of hyperthermia and radiation for superficial tumors[J]. Journal of Clinical Oncology, 2005, 23(13):3079-3085.
[3] Roti Roti J L. Cellular responses to hyperthermia (40-46 C):Cell killing and molecular events[J]. International Journal of Hyperthermia, 2008, 24(1):3-15.
[4] Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia[J]. Critical reviews in oncology/hematology, 2002, 43(1):33-56.
[5] Zhou J, Wang X, Du L, et al. Effect of hyperthermia on the apoptosis and proliferation of CaSki cells[J]. Molecular medicine reports, 2011, 4(1):187-191.
[6] Lo C M, Keese C R, Giaever I. Impedance analysis of MDCK cells measured by electric cell-substrate impedance sensing[J]. Biophysical journal, 1995, 69(6):2800.
[7] Nguyen T A, Yin T I, Reyes D, et al. Microfluidic chip with integrated electrical cell-impedance sensing for monitoring single cancer cell migration in three-dimensional matrixes[J]. Analytical chemistry, 2013, 85(22):11068-11076.
[8] Xie F, Xu Y, Wang L, et al. Use of cellular electrical impedance sensing to assess in vitro cytotoxicity of anticancer drugs in a human kidney cell nephrotoxicity model[J]. Analyst, 2012, 137(6):1343-1350.
[9] Wang L, Zhu J, Deng C, et al. An automatic and quantitative on-chip cell migration assay using self-assembled monolayers combined with real-time cellular impedance sensing[J]. Lab on a Chip, 2008, 8(6):872-878.
[10] Wang L, Yin H, Xing W, et al. Real-time, label-free monitoring of the cell cycle with a cellular impedance sensing chip[J]. Biosensors and Bioelectronics, 2010, 25(5):990-995.
[11] Giaever I, Keese C R. Monitoring fibroblast behavior in tissue culture with an applied electric field[J]. Proceedings of the National Academy of Sciences, 1984, 81(12):3761-3764.
[12] Wang L, Wang H, Mitchelson K, et al. Analysis of the sensitivity and frequency characteristics of coplanar electrical cell-substrate impedance sensors[J]. Biosensors and Bioelectronics, 2008, 24(1):14-21.
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