Abstract
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 Si3N4 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.
Highlights
The temperature of a single cell changes with its metabolic state and in response to external stimuli [1,2,3]
The functional region for cellular temperature detection in the newly designed chip consists of a temperature sensor array on a freestanding Si3 N4 thin film
Compared with semi-contact fluorescent thermosensitive probes, which use various fluorescent characteristics that are affected by the surrounding environment, the onchip freestanding thin-film thermocouple (TFTC) sensor chip we have developed measures the cellular temperature with a higher stability and is not affected by complex environments that include various ions, biochemical molecules, and a changing PH
Summary
The temperature of a single cell changes with its metabolic state and in response to external stimuli [1,2,3]. Accurate real-time temperature measurements of individual cells in different phases of their life cycles and in different external environments is important for understanding the internal connection between metabolism and cell function [4], as well as to promote research on organelle function [5], heat treatment of cancer [6], and drug screening [7]. The introduction of fluorescent materials may affect the normal metabolic activities of cells. Using different fluorescent probes, very different temperatures have been reported for HeLa cells, ranging from 1 K to 10 K above the ambient temperature [14,15,16,17,18]
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