Real-Time Cell Temperature Fluctuation Monitoring System Using Precision Pt Sensors Coated with Low Thermal Capacity, Low Thermal Resistance, and Self-Assembled Multilayer Films

Abstract

Real-time monitoring of cell temperature fluctuation can help researchers better understand physiological phenomena and the effects of drug treatment on cells, which is a novel and important tool for cellular informatics. The platinum (Pt) temperature sensor is widely used in temperature measurement with the advantages of strong stability, great accuracy, and high sensitivity. However, the commercially available Pt sensors have large thermal resistance and heat capacity which are difficult to be applied for cell temperature measurement because only a very small amount of heat flux is generated by live cells. In this study, we designed a system using precision Pt thin-film temperature sensors with low heat capacity and thermal resistance. The Pt thin-film sensors are covered by a silicon nitride insulation layer grafted with a self-assembled multilayer silane film for promoting cell adhesion. The temperature coefficient of resistance of the Pt temperature sensor was about 2100 ppm/°C. The four-wire lead design next to the sensor detection area ensured maximum accuracy, resulting in a system noise below 0.01 °C over a long time. HEK-293T and HeLa cells were cultured on the sensor surface, respectively. The temperature fluctuation of 293T cells was monitored in a cell culture medium, showing a temperature increase of about 0.05−0.12 °C. The temperature fluctuation of HeLa cells treated with cisplatin was also measured and recorded, indicating a temperature decrease of 0.01 °C first and then a gradual temperature increase of 0.04 °C. The Pt sensor system we developed demonstrated high sensitivity and long stability for cell temperature fluctuation monitoring, which can be widely used in cell activity and cellular informatics studies.

Advances in sensor developments for cell culture monitoring

“…(d) Reprinted with permission. Copyright 2023 from American Chemical Society [24] . (e) and (g) Reprinted with permission.…”

“…Copyright 2023 from American Chemical Society. [24] (e) and (g) Reprinted with permission. Copyright 2018 from Elsevier.…”

“…Zhang et al chose platinum thin film temperature sensors with a silicon nitride insulation layer grafted with self-assembled multilayer silane film for cell adhesion promotion (Figure 4d). [24] Notably, the RTD sensing system for the microscale volume-controlled sensing chip results in immediate and accurate performance that only works with proper calibration. Kim et al reported a multifunctional cell culture platform including a temperature sensor fabricated with graphene nanoribbons.…”

“…Recent advancements in analytical methods have supplemented traditional monitoring techniques, relying on an understanding and application of microfabrication, [17][18][19] optical [12,20] and conductive [21,22] materials, sensitive signaling probes, [5] and microfluidic chip packaging. [23,24] This review summarizes the parameters used for monitoring cell culture into four main categories: cellular physiology, cellular environment, cellular metabolite, and contaminant monitoring (Figure 1). The first category, cellular physiology, involves assessing various aspects of cellular viability, behavior, and related characteristics.…”

“…Several traditional methods have been employed to monitor cell culture, such as the optical microscope, spectrophotometer, chromatograph, electrical sensor, and a mass spectrometer. Recent advancements in analytical methods have supplemented traditional monitoring techniques, relying on an understanding and application of microfabrication, [17–19] optical [12,20] and conductive [21,22] materials, sensitive signaling probes, [5] and microfluidic chip packaging [23,24] …”