# Development of Highly Sensitive Temperature Microsensors for Localized Measurements  
[PERSON]  
1 Department of Industrial Electronics, Microelectromechanical Systems Research Unit (CMEMS-UMinho), Campus de Azurem, University of Minho, 4800-058 Guimaraes, Portugal; [EMAIL_ADDRESS] (V.C.P. ); [EMAIL_ADDRESS] (V.H.M. ); [EMAIL_ADDRESS] (R.O.R.) 2 Integrated Micro and Nanotechnologies, INL International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal; [EMAIL_ADDRESS]  
Cornespondence: [EMAIL_ADDRESS] (PJ.S. ); [EMAIL_ADDRESS] (G.M.) Faculty Engineering and Technology, University of Toronto, Toronto  
temperature in the cell culture. Furthermore, the frequency and duration of the incubator's door opening could induce temperature variations which can affect the cell culture. To overcome these limitations, temperature measurements within OoC are essential for ensuring that the most biological and chemical processes occur as ideally as possible [11]. This measurement must be effective and accurate, however, when the samples are of micro- or even of nano- order, as in OoC, this task becomes quite difficult [12]. Several approaches for cell culture temperature sensing have been explored in previous works such as commercial T-type thermocouples [13], NTC (negative temperature coefficient) thermistors [14], commercial PT-100 RTDs (resistance temperature detectors) [15], fluorescent polymeric thermometers [16] and optoacoustic methods [17]. However, conventional sensing devices for controlling the cellular microenvironment are not very compact for OoC applications and use expensive and bulky instrumentation equipment [11; 18]. Furthermore, optical temperature sensing has poor resolution (\(\sim\)1 \({}^{\circ}\)C) and its integration is complex [11]. The recent innovations in microtechnologies allow the development of miniaturized sensors and actuators with potential to be integrated within OoC. The small size of temperature sensors based on RTDs as well as their easy integration make them excellent candidates for applications in microfluidic-based devices, such as OoC. RTDs, as pointed out by their name, explore the electrical resistance variation, caused by temperature change. Furthermore, this sensor type provides a highly linear and sensitive response, covering large temperature ranges between \(-\)200 and 850 \({}^{\circ}\)C [19]. This work presents the development of temperature microsensors based on RTDs, which are designed to be integrated in an advanced OoC, allowing real-time and in-situ monitoring with a resolution of 0.1 \({}^{\circ}\)C in the range of physiological (35 \({}^{\circ}\)C) to hyperthermia (45 \({}^{\circ}\)C) temperatures [20]. Numerical simulations were performed to optimize the layout that better fits in the required application and to evaluate the sensor response according to different RTD dimensions. The results show that the platinum-based microsensor with a meander-shaped geometry (24 windings) offered the best sensitivity to temperature changes. Platinum is the best material for RTD, when compared with gold, copper, silver and aluminum, due to its highly linear response of its electrical resistance according to the temperature changes, high chemical resistance, high mechanical hardness, high temperature stability with a high melting point (1771.85 \({}^{\circ}\)C) and highly biocompatible [21; 22]. Using clean room microfabrication technologies, several sensors were fabricated, with different numbers of windings in a meander-shaped geometry, in order to assess the optimal number of windings that enabled the best performance of the sensor. Experimental results were compared with those obtained from numerical simulations. In addition, the electronic system for the sensor supply and data acquisition was developed. The temperature microsensors were designed to be integrated in a circular culture chamber of the OoC with a diameter of 15 mm, as showed in Figure 1. In doing so, the precise and local temperature of the organ models can be assessed.