Cell temperature measurement based on micro/nano materials and devices

Abstract

<p indent="0mm">In a complex, compartmentalized cellular environment, in order to maintain the concentration gradient and the dynamic balance of the cell itself, many biochemical reactions will take place inside the cell all the time, releasing free energy to drive various cellular activities. During cellular activity, a lot of information reflecting the detailed characteristics of cell activity is transmitted to the outside world, among which temperature information has sparked the increasing interest of many researchers in the field of cell temperature measurement. In the last decade, a number of researchers have developed a variety of micro-nanometer temperature sensors that would pave the pathway for accurate measurement of temperature or temperature distribution within cells and further unravel the mechanism of heat generation in mitochondria, endoplasmic reticulum, centrosome and other organelles or in the nucleus. Cell temperature sensors of micro-nano scale can be generally divided into cell temperature measurement by luminescence method and by pole probing method. Cell temperature measurement by luminescence method mainly includes organic compounds, quantum dots, polymers and biomolecules used as thermometers. Cell temperature measurement by pole probe method mainly includes thermocouple, platinum resistance and carbon nanotubes. This paper reviews the development of cell temperature measurement sensors at the micro- and nano-scale in recent years, and then focuses on the real-time cell temperature measurement technology of micro- and nano-thermocouple, and finally introduces the application of such sensors in the fields of drug screening, disease diagnosis and treatment, and foresees the prospect of the subsequent development of cell temperature measurement technology. This review lays emphasis on the importance of temperature in the physiological activities of cells and outlines the significance of temperature analysis and measurement at the single cell level. In biology, it is well known that temperature changes are susceptible to either cellular activity or responses to external stimuli, thus enabling the temperature and temperature gradient to determine the behavior of cells. Therefore, the kind of capability to monitor temperature with high spatial resolution (nm) and temporal resolution (μs) has become an essential tool for understanding specific biochemical processes and ideally designing target-specific diagnostic and therapeutic strategies such as hyperthermia and immunotherapy. To date, substances such as organic compounds, quantum dots, polymers and biomolecules that are particularly apt for making temperature measurement tools have made great progress, yet it is worth noting that problems still persist. For example, there is a dearth of consideration of the photo bleaching impact when it comes to the temperature measurement tools that are dependent on the fluorescence intensity; the quantum dot temperature measurement method itself also has enduring problems such as uneven luminescence and cytotoxicity; the process of introducing nano-diamonds into cells needs to take into account factors such as interference and complicated operational processes; biomolecules, issues surrounding its accuracy, must be addressed. The temperature measurement method, represented by the pole probe, is often limited by its preparation. The development of cell thermometers is dependent on cross-disciplinary efforts such as biology, microelectronics, materials science, thermodynamics, and nanotechnology. The concerted effort stands at the core of its future development of cell temperature measurement. Cell temperature measurement technology needs to fully explore its potential value, transforming the intracellular temperature signal into effective biological information, and applying it to drug screening, disease diagnosis and treatment, and bio-thermodynamic analysis. In the near future, cell temperature measurement technology will make tremendous contribution to the study of the principles of intracellular thermodynamics.