细胞是生命体的最小结构和功能的单位，细胞的生长、分裂、新陈代谢, 都从一个侧面反应生命体的生命状态和健康程度。而在这些生命过程中，伴随着物质转移和能量的转化，因此细胞内局部的温度可能会发生微小的变化。为了检测这一微小的温度信号变化，我们设计制作了微纳热电偶测温探针，其seebeck系数为4.6μV/K~10.2μV/K, 通过模拟得到探针的热响应时间约为400ns。
我们将探针插入U251脑胶质瘤细胞内并对其进行温度探测，使用两种抗癌药物喜树碱和阿霉素对细胞进行刺激，并在喜树碱组中探测到温度上升，以及上升过程中温度剧烈的变化。而在阿霉素组中却未发现温度上升。这一差别很可能是由于两种药物作用机理不同导致，因此监测细胞对药物刺激时温度的变化，有可能为药物筛选提供新的研究方法。
Changling Wang, Ruizhi Xu, Wenjuan Tian, Xiaoli Jiang, Zhengyu Cui, Meng Wang, Huaming Sun, Kun Fang and Ning Gu,
Determining intracellular temperature at single-cell level by a novel thermocouple method, Cell Research (2011) 21:1517-1519
Figure 1 (A) SEM image of tungsten probe coated by polyurethane (PU; except at the tip which is uncoated). (B) SEM image of the thin platinum film as an outermost layer. (C) Curves of the thermoelectric power from 0 °C to 90 °C. Red, green, and blue curves represent the thermoelectric power of the regular bulk W-Pt thermocouple, TC probe with 100-nm thick Pt film, and TC with 50-nm thick Pt film, respectively. (D) Optical microscopic image of a living U251 cell inserted by the TC probe. (E) A column figure indicating the average temperature changes for total cells after two drug treatment. (F) The simulated results of the TC probe response to a cell 2 °C higher than the environment. (G) Upper panel, a typical curve showing the changes of the intracellular temperature of a single U251 cell after CPT treatment. (a) TC inserted into the cell, (b) addition of CPT, and (c) TC withdrawn from the cell. Lower panel, a typical curve showing no temperature changes after addition of DOX. (a) TC inserted into the cell, and (b) addition of DOX. (H) A higher-resolution plot of part of the curve shown in (G) upper panel.
