Non-Interventional and High-Precision Temperature Measurement Biochips for Long-Term Monitoring the Temperature Fluctuations of Individual Cells

• Published in: Biosensors (Basel) Vol. 11; no. 11; p. 454
• Main Authors: Han, Danhong, Xu, Jingjing, Wang, Han, Wang, Zhenhai, Yang, Nana, Yang, Fan, Shen, Qundong, Xu, Shengyong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.11.2021; MDPI
• Subjects: Ambient temperature; biochip fabrication; Biochips; Biosensing Techniques; cell metabolism; Cell proliferation; cell temperature; Cellular stress response; Chemical composition; Control systems; Design; Drug metabolism; Drug screening; External stimuli; Fluctuations; Fluorescence; Fluorescent Dyes; Fluorescent indicators; Glass substrates; Heat; Heat stress; HeLa Cells; Humans; Life cycles; Metabolism; Monitoring; non-interventional biosensors; Plasma etching; Quantum dots; Sensors; Silicon nitride; Single-Cell Analysis; single-cell temperature measurement; Stimuli; Temperature; Temperature control; Temperature measurement; Temperature sensors; Thermocouples; Thin films; United States > US; Germany; cell metabolism; cell temperature; temperature sensors; biochip fabrication; non-interventional biosensors; single-cell temperature measurement
• ISSN: 2079-6374; 2079-6374
• DOI: 10.3390/bios11110454

Monitoring the thermal responses of individual cells to external stimuli is essential for studies of cell metabolism, organelle function, and drug screening. Fluorescent temperature probes are usually employed to measure the temperatures of individual cells; however, they have some unavoidable problems, such as, poor stability caused by their sensitivity to the chemical composition of the solution and the limitation in their measurement time due to the short fluorescence lifetime. Here, we demonstrate a stable, non-interventional, and high-precision temperature-measurement chip that can monitor the temperature fluctuations of individual cells subject to external stimuli and over a normal cell life cycle as long as several days. To improve the temperature resolution, we designed temperature sensors made of Pd-Cr thin-film thermocouples, a freestanding Si N platform, and a dual-temperature control system. Our experimental results confirm the feasibility of using this cellular temperature-measurement chip to detect local temperature fluctuations of individual cells that are 0.3-1.5 K higher than the ambient temperature for HeLa cells in different proliferation cycles. In the future, we plan to integrate this chip with other single-cell technologies and apply it to research related to cellular heat-stress response.