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A Body Compatible Thermometer Based on Green Electrolytes Xinglei Tao, Shenglong Liao, Shuqiang Wang, Di Wu, and Yapei Wang ACS Sens., Just Accepted Manuscript • DOI: 10.1021/acssensors.8b00249 • Publication Date (Web): 15 Jun 2018 Downloaded from http://pubs.acs.org on June 21, 2018
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A Body Compatible Thermometer Based on Green Electrolytes Xinglei Tao, † Shenglong Liao, † Shuqiang Wang, ‡ Di Wu, ‡ Yapei Wang* † †
Department of Chemistry, Renmin University of China, Beijing, 100872, China
‡
Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing 100853, China KEYWORDS: Thermometer, green electrolytes, biocompatibility, nontoxicity, body temperature. ABSTRACT: With the use of coordinated complex between aliphatic diols and calcium chloride (CaCl2) as green electrolytes, a body compatible, eco-friendly and low-cost thermometer is successfully developed. This particular conductive liquid possesses unique features of ultrafast response and high sensitivity against temperature change. The influences of CaCl2 concentration and the category of aliphatic diols on conductivity change reveal that the thermal sensing abilities of such a kind of green electrolytes are positively relevant to the viscosity change along with temperature change. Owing to the advantages of stability, reliability, and security, the thermometer can implement long-term and continuous temperature monitoring, which can fully meet the requirements of application of medical monitor, diagnostics and therapies. Moreover, the inherent advantages of thermometers, including satisfactory biocompatibility and nontoxicity, afford great promise for applications in invasive and inflammatory devices.
Past several decades witnessed explosive development of bioelectronics which have shown great potential in healthcare, especially physiological monitoring systems including electrocardiogram, blood pressure, pulse, temperature, oxygen partial pressure.1-6 With increasing efforts on the development of wearable or implantable electronic sensors, a numerous number of sensing materials have been exploited, mainly formulated by metallic materials,7,8 semiconducting metal oxides,9 carbon-based materials,10,11 conducting polymers.12-15 These solid-state sensing materials have already been at the forefront of intensive investigation due to their comparatively mature processing flow, precise measurement and low cost. In terms of excellent deformability and facile recycling of liquid materials, liquid electronics based on electrically conductive liquids including ionic liquids and liquid metals are forming a new research field when considering their advantages of high flexibility, self-healing ability and capacity of doping/being doped with other functional materials. Many researches on flexible, self-healing electronics and multifunctional sensors were established via the efficient integration of liquid materials with elastomeric scaffolds, self-healing polymers and functional dopants.16-19 The unique fluidic feature offers great convenience for high-throughput fabrication of cheap sensors based on inkjet printing technique.20 In addition, ionic liquids could also overcome modulus mismatch between sensing materials and flexible substrates to realize reliable and long-term stable measurement.21 Liquid electronics are hopefully to serve as alternatives to traditional solid electronics intending for medical diagnosis with special requirements. However, the study of liquid electronics is still at an infancy stage because of the limited species of sensing fluids for now. Only ionic liquids have been successfully exploited as the liquid sensing fluids so far, which are yet lack of biocompatibility and far from straightforward body compatible applications.
In order to adapt liquid sensing materials to biological applications, four essential features including nontoxicity, rapid degradability, good stability and excellent sensing performance should be taken into account. Herein, a kind of green electrolytes composed of aliphatic diols and calcium chloride only were designed as nontoxic, biodegradable and thermalsensitive fluids. Specifically, aliphatic diols, such as ethylene glycol (EG), dissolving CaCl2 as a green electrolyte, was encapsulated in polylactic acid (PLA) chips to obtain biocompatible, eco-friendly and low-cost thermometers with merits of high sensitivity and ultrafast thermal response. Such a thermometer can fully meet the requirements of real-time temperature monitoring system. Meanwhile, the notable stability, reliability, and security of the thermometer ensure long-term and continuous temperature measurements for medical diagnostics and therapies. Moreover, the inherent advantages of thermometers, including biocompatibility and nontoxicity, afford great promise for implantable biosensors with low level inflammatory. To the best of our knowledge, this is the first body compatible electronic sensor made of biocompatible liquid sensing materials, which opens up new opportunities for health monitoring and medical diagnosis.
EXPERIMENTAL SECTIONS Materials. Polylactic acid (PLA, 2002D) was purchased from Nature Work. Calcium chloride, ethylene glycol, 1,2propylene glycol, 1,3-propylene glycol, 1,2-butanediol, 1,3butanediol, 1,4-butanediol, 2,3-butanediol, and 1H,1H,2H,2Hperfluorooctyl trichlorosilane were provided by Shanghai Aladdin Bio-Chem Technology Co., Ltd. Rhodamine B (RhB) is commercially available from Beijing Chemical Reagent Company.
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Fabrication of electronic sensors. The glass with double spiral embossment was fabricated through standard photolithography and wet etching techniques.22 A piece of 4 inch square glass coated with a middle layer of chrome (100 nm) and a top layer of positive photoresist (700 nm, RJZ-304) was provided by Microcad Photomask Ltd. The glass closely contacted with a common photomask was exposed to UV light for 30 seconds. Then, the exposed photoresist was removed by NaOH solution (0.5 wt.%) and chrome was removed via rinse with chrome etchant (ammonium ceric nitrate (20 wt.%) and acetic acid (0.6 mol/L)). The next step in the fabrication procedure is to etch the glass in a well-stirred bath containing etchant of HF (1 mol/L), NH4F (0.5 mol/L) and HNO3 (0.75 mol/L) at 40 °C with a steady etching rate of 1 µm/min for about 4 hours. The glass was cleaned by piranha solution and then modified with 1H,1H,2H,2H-perfluorooctyl trichlorosilane. The PLA slices with microchannel were replicated by common hot-pressing method.23 Firstly, commercial PLA particles were placed on the glass with double spiral embossment at 180 °C. Then, the particles were covered with smooth glass and pressed into slices with the help of a pressure gauge (MARK-10, Series 5, USA). To ensure PLA slices with uniform sizes, the mass of PLA particles and the squeezing pressure were kept at given values. Other PLA slices without microchannel were prepared via the same method with two pieces of smooth glasses. Subsequently, the two pieces of PAL slices adhered together via a constant temperature heating stage (IKA C MAG HS7) at 90 °C. Finally, the solution was injected through the microchannel via the inlets and two electrodes were inserted into the inlet and outlet. Characterization. Fourier transform infrared (FTIR) spectra were recorded on a Bruker Tensor 27 spectrometer with a scanning resolution of 4 cm-1 and a scanning number of 64 from 400 to 4000 cm-1. Differential scanning calorimetry (PerkinElmer DSC8000) was utilized to determine the melting point of PLA. The temperature was controlled by constant temperature heating stage and thermal responses of these electrolyte solutions were collected by a CHI660e electrochemical workstation (Shanghai CH instrument Co., Ltd). The electrical conductivities of these solutions were measured by a conductivity meter (DDS-307A, Shanghai INESA Scientific Instrument Co., Ltd.). The viscosities of these solutions were collected by a viscometer (Lovis 2000 M/ME, Anton Paar Shanghai Trading Co., Ltd). Monitoring of body temperature. In order to precisely measure the body temperature, the thermometer was electrically connected with a CHI660e electrochemical station to obtain a standard curve of the relationship between the thermal response and body temperature. A constant temperature heating stage provided a range of temperature with a minimum step heating rate of 0.5 °C. With a given temperature difference, thermal response of the thermometer connected with electrochemical workstation was tested through AC impedance-time method. The temperature increases to the setting value and decreases to room temperature alternatively with a period of 2 minutes. Subsequently, the thermometer was put under the armpit of the body and the body temperature was calculated according to the standard curve as previous calibrated. Measurement of in vivo temperature of a mouse and the histological study of implantation of the body compatible sensor. The supply of eight-week-old C57BL/6 male mice was governed by the Experimental Animal Center of the
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Academy of Military Medical Sciences. The mice were fed with adequate standard rodent chow and water at a constant temperature in a 12-hour light/dark cycle. The animals were acclimated for seven days before initiating the experiment. All animal protocols were approved by the Animal Ethics Committee of the Chinese People's Liberation Army General Hospital and Military Medical College.24,25 The edge of the sensor was smoothed with a commercial laser cutter (Shandong Liaocheng Tianlang Laser Technology Co., Ltd) and the sensor was soaked in 75% alcohol before implantation. Then, incisions were made at the skin of back neck and subcutaneous pocket was created by blunt dissection with haemostatic forceps, and the thermometer was inserted into the pocket. Thermal responses of the thermometer were measured by a CHI660e electrochemical workstation and the in vivo temperature of the mouse was calculated according to the standard curve as stated above. Finally, the part of the sensor with outer skin was clipped and the wounds were carefully closed. Implants were extracted together with the surrounding tissues 2, 4, and 6 weeks postsurgery. Subsequently, the surrounding tissues were fixed with 10% formalin and embedded in paraffin. Cuts were carried out with a paraffin microtome. These sections were stained with Haematoxylin-Eosin (H&E) and examined by optical microscopy.
RESULTS AND DISCUSSION Intending for biocompatible liquid sensors, both sensing fluids and supporting matrix are required to be nontoxic, biodegradable and environmental-friendly. Herein, as shown in Figure 1a, aliphatic diols dissolving certain amount of calcium chloride are selected as sensing materials and polylactic acid is chosen as the substrate materials, both of which satisfy the demand for body biocompatible applications. As a typical thermoplastic polymer, polylactic acid can be easily molded into desired patterns. According to the DSC curve (Figure S1a), PLA chips were molded at a suitable temperature (180 °C) above its viscous flow temperature and sealed at a lower temperature (90 °C) that is higher than glass transition temperature. This solvent-free fabrication method ensures PLA chips have not been involved with other chemical residuals. The green electrolyte composed of aliphatic diols and calcium chloride was loaded into a PLA chip through injection method. Prior to conducting electrical testing, photographs of the PLA chips loading sensing liquid were taken by singlelens reflex camera (Figure 1b and 1c) and fluorescence microscope (Figure 1d), which clearly exhibit a continuous doublespiral liquid channel without any bubble or air plug. Thus the biocompatible thermometer was successfully fabricated and then it can be used for temperature sensing tests by connecting with electrical power source and signal measurement unit. A typical thermometer with electrolyte composed of EG and calcium chloride was firstly tested for thermal sensing performance, and the results as shown in Figure 1e indicate that the conductivity of the sensor obviously varies as the temperature changes. To quantify the thermal sensing ability of the thermometer against temperature change, the thermal response was defined as the relative change of conductivity ∆ ⁄ (%): ∆
(%) =
× 100
(1)
where and are the initial conductivity and current at room temperature, respectively, and refers to the real-time
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Figure 1. Fabrication procedure and thermal sensing property of the body compatible sensor. (a) Schematic illustration of the fabrication process of the body compatible sensor. (b) Optical image and (c) Fluorescent image of a body compatible sensor. The blue dotted box region marked in (d) is magnified as microscope image of (c). (e) The relationship between thermal responses and temperature of a typical green electrolyte composed with EG and CaCl2. current in the measurement process. As shown in Figure 1e, thermal response of a typical thermometer was tested under different temperatures. Remarkably, the thermal response reaches 54.27% as the ambient temperature increases from room temperature (25 °C) to 40 °C. Compared with other reported sensing materials or thermometers (Table S1),26-28 the as-prepared biocompatible thermometer exhibits good thermal sensitivity, which is necessary for next generation of highperformance bio-electronic devices. To fabricate a high-performance and stable thermometer, two factors including the concentration of CaCl2 and the kind of aliphatic diols were come into focus for studying their impact on the conductivity and the sensing ability. Thermal responses of EG dissolving CaCl2 with different concentrations were firstly tested. As shown in Figure 2a, the results illustrate that with increasing the concentration of CaCl2, the thermal response of EG keeps almost the same at lower concentrations and increases slightly at higher concentration. In this regard, the concentration of solute is hardly involved in determining the thermal sensing properties of thermometers, which may only relies on the kind of solvent. Thus, six aliphatic diols, with different alkyl chain lengths or the different positions of the hydroxyl group, were studied for their influence on thermal response of EG. As shown in Figure 2d, six kinds of ali-
phatic diols exhibit distinctly different thermal sensing ability. However, with the increase of alkyl chain length or the position change of alcohol groups, the thermal response of these aliphatic diols does not follow a reasonable regularity. Hence, the relationship between thermal sensing ability and chain length of aliphatic diols or the position of hydroxyl group is still unclear based on the above thermal sensing tests. Notably, we also investigate the influence of channel length of green electrolyte on thermal response. It is found that the channel length may correlate with the resistance of sensing fluid, but hardly make any influences on thermal response (Figure S2). As the definition of thermal response is based on the relative change of conductivity, it is reasonable to assume that thermal response should be correlative with the relative change of conductivity, which is one of the basic physical properties of a specific electrolyte. To clarify the mechanism that affecting the thermal response, conductivities of thermal sensing electrolytes as stated above were measured by a conductivity meter stepwise from room temperature to 60 °C. The results as summarized in Figure 2b and 2e indicate that the conductivity increases with the increase of temperature. Herein, thermal response calculated according to the relative change of con ductivity is defined as follows:
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Figure 2. Evaluation of thermal sensing properties for the body compatible sensors. (a) Thermal responses of EG in the presence of CaCl2 with different concentrations of 0.01 mol/L, 0.05 mol/L, 0.10 mol/L, 0.20 mol/L, 0.30 mol/L, 0.50 mol/L and 1.0 mol/L, respectively. (b) The electrical conductivities of EG dissolving different concentrations of CaCl2. (c) The thermal responses calculated with the measured electrical conductivities in (b). (d) Thermal responses of six aliphatic diols, including EG, 1,2-propanediol, 1,2-butanediol, 2,3-butanediol, 1,3-propanediol and 1,4-butanediol. The concentration of CaCl2 and room temperature are fixed as 0.01 mol/L and 25 °C, respectively. (e) The electrical conductivities of six kinds of aliphatic diols dissolving 0.01 mol/L CaCl2 at different temperatures. (f) The thermal responses calculated with the measured electrical conductivities in (e). ∆
,
=
()
1
(2)
where , and σ are the initial electrical conductivity and conductivity at room temperature, respectively, and ( ) is the conductivity at a certain temperature of . According to this equation, thermal responses were calculated as shown in Figure 2c and 2f. It is worth noting that electrical conductivity measured on a conductivity meter (Figure 2b and 2e) has a consistent trend with thermal responses (Figure 2c and 2f), which was expected to agree with previous assumption. To further evaluate the thermal response of body biocompatible thermometer as function of temperature change, great insights were provided to the conductivity mechanism of electrolyte. According to the equilibrium between the friction drag force and the electric force as shown in Equation (3), ion migration as the core process accounting for the electrical conductivity is often affected by the ionic radius, charge number, number of ions, intensity of electrical field and liquid viscosity. = 6 !"# = $% |'| (3) where represents the friction drag force or the electric force; " and # represent the radius and the migration velocity of ions in electrolyte; $% represents the charges of the ions; |'| represents the intensity of electric field; ! represents the liquid viscosity. Since the first four factors are not sensitive to temperature, it can be inferred that the thermal sensing ability is only attributed to the viscosity change under different temperature. Commonly, the relationship between the viscosity and the temperature ( ) is referred as Andrade’s equation:29 ()! = * +
,
(4)
where * and - are constants. As shown in Figure 3a and 3c, the viscosity change as function of temperature perfectly fits Equation (4). When EG is selected as the solvent dissolving CaCl2 with different concentrations, the slopes in Figure 3a fitted according to Equation (4) exhibit negligible difference. As shown in Figure 3b, thermal response of EG dissolving different concentrations of CaCl2 are almost the same, consistent with above deduce that the thermal response is only contributed to viscosity change. While for different aliphatic diols with the same concentration of CaCl2, the slopes calculated according to Andrade’s equation are distinctly different, leading to different thermal sensing abilities. Among the six kinds of aliphatic diols, 2,3-butanediol dissolving CaCl2 (0.01 mol/L) with the largest slope has the highest thermal response value (Figure 3d). Based on these results, it is reasonable to draw a conclusion that the thermal sensing performances of above green electrolytes are only determined by the viscosity change along with temperature change and a larger slope value from Andrade’s equation can lead to better thermal sensitivity. Although the highest thermal response of green electrolytes could be obtained by employing 2,3-butanediol and high CaCl2 concentration, biocompatibility and biosafety are always the prime elements needed to be considered in the design of bio-electronics, especially in biocompatible thermometers. Notably, EG is a kind of much safer fluid compared with other aliphatic diols. In the following section, EG instead of other aliphatic diols was chosen as the green solvent to dissolve CaCl2 for the fabrication of biocompatible thermometer. As a biocompatible thermometer, other thermal sensing parameters including temperature resolution, linearity, response speed, repeatability and stability are also needed to be evaluated for further practical applications.30-32 First, to explore the
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Figure 3. Relationship between thermal response and viscosity change of green electrolytes at different temperatures. (a) Relationship between viscosity and temperature of EG dissolving CaCl2 in different concentrations. (b) Fitted slopes through Equation (4) and thermal responses of EG dissolving different concentrations of CaCl2 at 50 °C. (c) Relationship between viscosity and temperature of six kinds of aliphatic diols dissolving 0.01 mol/L CaCl2. (d) Relationship between of thermal responses of six aliphatic diols with 0.01 mol/L CaCl2 at 50 °C and the corresponding slopes of Equation (4) in 3c. application of thermometer in monitoring body temperature, excellent temperature resolution is essential as well as the thermal sensitivity. As shown in Figure 4a, on-off thermal response is achieved under alternately heating and cooling operations. A significant thermal response change (3.906%) is reached at a given temperature difference (1.0 °C). Moreover, with a lower temperature difference (0.5 °C) established, the difference of corresponding thermal responses is clearly exhibited as shown in Figure 4b. Based on the thermal response from 30 °C to 40 °C, a standard curve can be figured out by linear fitting as plotted in Figure 4a. The linear fitting results revealed a perfect proportional relationship between thermal response and temperature, which is a solid advantage of this biocompatible thermometer. Hence, real-time body temperature could be easily achieved by reading thermal response value in the practical application. Another interesting phenomenon in Figure 4a & 4b is that the thermal response increases immediately upon temperature change due to the short thermal conduction distance between sample and sensing elements. As magnified in Figure S2b, the response time against thermal heating is about 8 seconds, which is shorter than any liquidbased sensors reported before.18 Such a rapid thermal response plays an essential role in real-time temperature monitoring applications. Moreover, it is notable that none failure of the thermometer happens and the thermal response is maintained within a steady level at a given temperature for over two months (Figure 4c), which promises long service life in further applications. Due to the existence of circadian rhythms, intensities of different biological activities vary day and night, leading to a
diurnal variation of body temperature. On the contrary, the variation of body temperature can also reflect some biological activities such as sleeping, eating or drinking.33-35 Herein, the body compatible thermometer is applied for real-time monitoring of body temperature. As illustrated in Figure 4d and 4e, the thermometer was attached onto armpit of a volunteer and connected with an electrochemical workstation. Two volunteer tests with different diet conditions in morning were carried out from 9:00 am to 12:00 am. The real-time body temperature was recorded in Figure 4g. The red curve, representing that the volunteer had breakfast before the test, appears an obvious decline before slight increase as testing time goes on, while the other black curve exhibit a continuously slow increase in the whole monitoring process. The slight decrease of body temperature after having breakfast as the exact difference between these two tests, possibly results from the energy consumption for digestion.36 To further verify the potential for long term practical application, the body compatible thermometer was applied to monitor the menstrual cycle of a female volunteer for 40 days. The results plotted in Figure 4h present a periodic temperature change of the female volunteer, including a higher temperature period in follicular phase (FP) and a lower temperature period in luteal phase (LP). The tested FP and LP perfectly matches with the menstrual cycle of this female volunteer whose FP and LP period start from day 6 and day 21, respectively. Above results indicate this body compatible thermometer could detect human activities such as diet condition and menstrual cycle via real-time and long-term temperature monitoring, offering a powerful tool for human health testing and caring.
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Figure 4. Real-time monitoring of body temperature by the body compatible sensor. (a) On–off cycles of thermal response (black line) and the thermal response value (red line with dots) of body compatible sensor against the increase of temperature ranging from 30 °C to 40 °C with an interval of 1 °C. Room temperature is 25 °C. The calculated equation of the fitting curve is marked with a blue box. (b) Real-time temperature measurement via the body compatible sensor according to the equation in (a). The measured temperature changes from room temperature to a given temperature (ranging from 35 to 37 °C with an interval of 0.5 °C) repeatedly. (c) Long-term test of thermal sensing stability from room temperature to 35 °C. (d-e) Schematic illustration of real-time in vitro monitoring of body temperature. The blue dotted box region marked in (d) is magnified as an image in (e). (f) On-off cycles of the thermal response between in vitro body temperature and room temperature. (g) Real-time monitoring of in vitro body temperature of a volunteer without breakfast (black) or with breakfast (red). (h) Temperature measurement of a female volunteer at 5 pm every day. The follicular phase (FP) and luteal phase (LP) tested according to the temperature variation are clarified by blue and red regions. To further extend the potential application, the body compatible thermometer is also adopted in monitoring temperature in vivo.37 As shown in Figure 5a and 5b, the thermometer was implanted under the skin of a mouse to monitor the temperature after the mouse was anesthetized. As a result, the in vivo temperature of the mouse drops sharply in the first 10 minutes due to the decreased basic metabolism caused by anesthetic effect. Then, the body temperature increases due to thermoregulation via shiver for self-protection. Finally, the temperature remains slight fluctuation until the mouse is fully revived (Figure 5c). As an important factor for implantable devices, biocompatibility of electronic sensor is crucial for in vivo application. To investigate the biocompatibility of the thermometer, the immune inflammatory response of mice was tested at different implantation time (2, 4, and 6 weeks). Fig-
ure 4d-i showed histological sections of tissue around the thermometer 2, 4, and 6 weeks after surgery. During 2 weeks after implantation, immune cells such as neutrophils and lymphocytes migrated to the connective tissue at the surface of the sensor and this was accompanied by angiogenesis around the sensor. 4 weeks after implantation, the inflammatory cells were reduced and the connective tissue got fibration. 6 weeks after implantation, the inflammatory response was disappeared and the fibrous capsule of sensor became denseness. Furthermore, the absence of inflammatory cells was noted in the adipose and muscular tissue after 2 weeks (Figure S3). The above results indicate that the thermometer exhibit negligible toxicity, immunogenicity and desirable biocompatibility in in vivo tests, which is qualified as an implantable electronic sensor.
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Figure 5. Real-time monitoring of in vivo temperature by body compatible sensor and the biocompatibility testing of the sensor. (a) Schematic illustration of testing site of a mouse. (b) Photograph of a sensor implanted into the mouse after anesthesia and testing the in vivo temperature. (c) Real-time monitoring of in vivo temperature of the mouse after anesthesia. (d-i) H&E staining of histological sections 2 weeks (d, g), 4 weeks (e, h) and 6 weeks (f, i) after the sensor was implanted into the mouse. Blank region marked with blue letter “S” means the sensor place that directly contacting the tissues. The green dotted box region marked in (d), (e), and (f) is magnified as a photomicrograph image in (g), (h), and (i), respectively.
CONCLUSIONS
ASSOCIATED CONTENT
In summary, we have successfully developed a kind of body compatible and eco-friendly thermometer with the use of green electrolytes as sensing liquids. The thermometer based on EG dissolving calcium chloride exhibits extremely high thermal sensitive and can precisely monitor body temperature for long time with stable sensing performance. The sensing fluids exhibit other advantages including good linearity, longtime stability, nontoxicity and body compatible. Moreover, via real-time temperature monitoring, the body compatible thermometer can reflect some physiological activities or signals of the human body such as eating, digesting and menstrual cycles of the female. As a body compatible thermometer, it can be served as an ideal alternative for in vitro or in vivo temperature measurements. By introducing more functional sensing elements in this system, it is absolutely promising that our device exhibits great potential for wearable and implantable bioelectronics devices where body compatible sensors are highly desired.
Supporting Information The following files are available free of charge on the ACS Publication website at http://pubs.acs.org The FT-IR spectrum; DSC thermograms; The thermal response with different length; The cyclic thermal response; The histological staining; Comparison with other temperature sensors
AUTHOR INFORMATION Corresponding Author * E-mail:
[email protected] Author Contributions The manuscript was written with the contributions of all authors.
Notes The authors declare no competing financial interest.
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ACKNOWLEDGMENT This work was financially supported by the National Natural Science Foundation of China (21422407, 51373197, and 21674127). Miss Ruiting Li and Miss You Zhou are acknowledged for their volunteer contribution on body temperature measurements.
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