Summary of the properties of the different SThM probes mentioned in the text.
\r\n\tTherefore, the objective of this book is to provide an outlook of the present research on Applied Geomorphology in different parts of the world, highlighting the main challenges mankind faces on this subject. The debate on future perspectives of anthropogenic impacts on the Earth surface and systems, the evolution of concepts on Applied Geomorphology, processes and landforms evaluation and modeling, recurring to recent technologies and methods, geomorphological hazard analysis, as well as strategies for landform conservation and promotion (for non-extractive and destructive activities, e.g. geotourism), are also objectives to pursuit on this book.
",isbn:"978-1-80356-423-4",printIsbn:"978-1-80356-422-7",pdfIsbn:"978-1-80356-424-1",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"f9f0fe8910dc02818cad71316650d297",bookSignature:"Prof. António Vieira",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11491.jpg",keywords:"Theory, Processes, Methodologies, GIS, Remote Sensing, UAV, Human Impact, Anthropocene, Slope Instability, Climate Change, Geomorphosites, Geotourism",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 25th 2022",dateEndSecondStepPublish:"April 27th 2022",dateEndThirdStepPublish:"June 26th 2022",dateEndFourthStepPublish:"September 14th 2022",dateEndFifthStepPublish:"November 13th 2022",remainingDaysToSecondStep:"24 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A geographer with a career of more than 20 years devoted mainly to geomorphological research, centered in the topics of granitic geomorphology, soil erosion, and geomorphological heritage, and responsible for Ph.D. and Pos-doc researchers and for research project leadership. He is an assistant professor in the Department of Geography, University of Minho (UM), Portugal, and an integrated member of the Communication and Society Research Centre (CECS), UM.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"103627",title:"Prof.",name:"António",middleName:null,surname:"Vieira",slug:"antonio-vieira",fullName:"António Vieira",profilePictureURL:"https://mts.intechopen.com/storage/users/103627/images/system/103627.png",biography:"Antonio Vieira is a geographer with a Ph.D. in Geography from the University of Coimbra, Portugal (2009). He is an assistant professor in the Department of Geography, University of Minho (UM), Portugal, and an integrated member of the Communication and Society Research Centre (CECS), UM. 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A genome search using two FC families identified strong evidence for linkage to the locus on chromosome 16q12-q13 (Biggs et al., 1995). Subsequently, germline mutations in the tumor suppressor
In 2003, CYLD was shown as a deubiquitinating enzyme that negatively regulates nuclear factor-kappa B (NF-κB) activation (Brummelkamp et al., 2003; Kovalenko et al., 2003; Trompouki et al., 2003; Wilkinson, 2003). NF-κB is involved in controlling inflammation, the immune response, and apoptosis (Pasparakis, 2002). Nowadays, many different cellular functions have been ascribed to CYLD such as proliferation and cell cycle, Ca2+ channel signaling, survival and apoptosis, inflammation, T-cell development and activation, antiviral response, and spermatogenesis (Pasparakis, 2002).
CYLD contains three cytoskeleton-associated protein-glycine-rich (CAP-Gly) domains, two proline-rich motifs, a tumor necrosis factor-alpha (TNF-α) receptor-associated factor 2 (TRAF2) binding site, and ubiquitin-specific proteases (USP) domain responsible for its deubiquitinases (DUB) activity (Harhaj et al., 2011; Pasparakis, 2002). The first two CAP-Gly domains mediate binding to microtubules (Gao et al., 2008; Wickström et al., 2010), and the third CAP-Gly domain regulates NEMO interactions. NEMO (also known as IκB kinase gamma (IKKγ)) is the regulatory subunit of the IκB kinase (IKK) (Yoshida et al., 2011). IKK plays crucial role in activating NF-κB in response to various inflammatory stimuli (Zheng et al., 2011). TRAF2 regulates activation of the c-Jun N-terminal kinase (JNK)/c-Jun and the inhibitor of IKK/ NF-κB signaling cascades in response to TNF-α stimulation (Zhang et al., 2011).
In the last years, there has been a great improvement in thin film fabrication, with a reduction in the costs, and an enhancement in their quality and performance, as it is shown in the different chapters of this book. Therefore, there has been an increase in thin film applications in different fields [1], which take advantage of the modification of electronic and thermal transport when the dimensions of the material are reduced to lengths comparable to the mean free path of phonons and charge carriers. Thin films with tailored thermal and electrical properties are employed in solar cells [2], electronics [3], or thermoelectric conversion devices [4], among other fields. Nevertheless, the optimization of the materials for these applications requires measurement techniques that provide precise information of both the surface and the properties at the nanoscale, with high local resolution. In this sense, scanning probe microscopy (SPM) methods fulfill these requirements, with a high spatial resolution, strong sensitivity, and in most cases, no previous preparation of the sample is needed. In this chapter, we will focus on one type of SPM technique, namely scanning thermal microscopy (SThM). This technique allows to study the thermal transport phenomena at the nanoscale, providing a powerful tool to understand thermal properties of thin films.
\nHistorically, the atomic force microscope (AFM) was developed by Binning et al. [5] in 1986. The AFM was a new type of microscope that used the principles of the scanning tunneling microscope (STM) and the stylus profilometer (SP), allowing the investigation of both conductors and insulators at the atomic scale (which could not be characterized by STM before) by measuring interatomic and electromagnetic forces. Controlling the probe-sample gap by a feedback loop that kept constant the force between the probe and the sample during the scan, the topography of the sample was obtained from a contrast image given by the height of the probe at each point. In the same year, only a few months later, a new noncontact high-resolution surface characterization technique for topographic images was presented by Williams and Wickramasinghe [6], the scanning thermal profiler (STP). This was the beginning of the scanning thermal microscopy. In this case, the probe was conical, with a thermocouple nanojunction located at the end of its tip. The probe was then heated with a laser and brought close to the surface of the sample, where it was cooled down due to the heat transfer to the sample. In this case, the temperature of the probe was used in the feedback loop to control the gap between tip and sample, keeping the probe temperature constant while varying its height. Therefore, this information could not be used to provide thermal maps of the surface, but that was not the objective of this technique, which tried to improve the topographic images obtained by using the thermal interaction between the tip and the sample. In the next few years, different techniques based on probe scanning microscopies were developed to measure a variety of properties in the micro- and nanoscale: the scanning tunneling thermometer, which was able to measure with 1 nm spatial resolution the optical absorption of thin metal films, or to map the variations of the electrochemical potential at the nanometer scale [7, 8]; the so-called Kelvin probe force microscopy (KPFM), which provided the work function or surface potential of a sample [9], through the measurement of the contact potential differences. This principle was also used while scanning the surface with a heated sharp probe, obtaining a qualitative image of the changes at the subsurface on the thermal conductivity [10]. In this last work, dated in 1992, Nonnemacher and Wickramasinghe defined this period of time as one with “a tremendous growth in scanned probe microscopies” [10].
\nThe next breakthrough in the field took place in 1993 when Majumdar et al. went a step further. They replaced the AFM probe by two wires (chromel and alumel) to form a thermocouple junction at the tip and, when scanning the surface with this modified probe, they obtained simultaneously the thermal and topographical images with a sub-micrometric spatial resolution [11]. From this moment on, different groups started working on improvements on this type of measurements, such as Pylkki et al., who integrated a resistive thermal probe within an AFM cantilever, in order to measure both the actual temperature and the thermal conductivity [12]. These kinds of probes can work in two different modes, passive (where they act as a thermometer) or active (acting also as a heater), which will be discussed in detail later (Section 2). In the case of the first thermistor probe, the temperature of the probe was monitored by measuring the changes in its electrical resistance [12]. Further works explored the potential of this scanning thermal microscopy (SThM) technique to study the thermal response of thin films and nanostructures, using different designs for the AFM probes modified with a thermocouple to minimize the image distortion, temperature loss and, at the same time, increase the imaging resolution, as it was made by Majumdar et al. [13]. Nevertheless, it is worth to note that, at this point, the results obtained as far as the thermal properties were concerned, were more qualitative than quantitative, given that the models used were quite simple and did not take into account the geometry of the probes or the heat transfer characteristics when working in contact or noncontact modes. One of the first quantitative results was obtained in 1995 by Hammiche et al. They presented a work based on SThM performed with a Wollaston cantilever (please see Section 2) to obtain subsurface imaging of copper metallic particles embedded in polystyrene [14]. The thermal image was acquired in active mode, keeping the temperature of the probe constant. In this mode, the probe acts as a resistive heater that forms part of a Wheatstone bridge that, thanks to a feedback system, gives the appropriate voltage to maintain a constant temperature of the probe. In this work, they also developed a one-dimensional theoretical model to obtain quantitative information from the thermal maps, obtaining information of the depth at which the inclusions were, and thermal conductivity inhomogeneities. Although the results obtained did not match the expected thermal conductivity values and the precision of the location of the buried particles was very low, this was probably due to a too simple heat transfer model. But this paved the way for further and better theoretical models for these systems.
\nThe SThM started to be present in overview articles of thermal analysis in the following years, such as that published by Kölzer et al. [15], where different techniques used for thermal imaging of electronic devices were reviewed. The influence of thermal stresses in the performance and reliability of electronics, and thus the thermal characterization of micro- and nanoelectronic devices, is quite relevant to carry out the device optimization and avoid malfunctioning due to a bad management of heat. Among the different methods cited (thermography, optical beam displacement, thermoreflectance, etc.), near-field techniques as SThM were discussed as the best method to achieve the characterization at the micro- and nanoscale at high resolution (achieving down to 30 nm lateral resolution). In 1998, Gmelin et al. presented a review article on the evolution of SThM [16], which together with the extensive review written by Majumdar in 1999 [17] gives a complete overview of the state of the art of this method at the end of the twentieth century. At that point, the SThM technology was used for the thermal analysis of micro- and nanostructured materials and devices. In fact, Majumdar made a distinction between three different categories: SThM based in thermo-voltage, electrical resistance, and thermal expansion measurements. In this review, the different probes, experimental setups and specific applications for each of them are discussed. One of the most important issues to interpret the measurements performed by SThM is to understand the fundamental heat transfer phenomena between the tip and the sample, which controls the resolution, accuracy, and artifacts. Therefore, the mechanics of heat transfer are also reviewed in depth in this work.
\nA further breakthrough in SThM was achieved in 1999 by Fieged et al. when they combined an SThM with the 3\n
The latest improvements in the SThM technique have come from studying in depth on how different materials react to local temperature rises. The heat transfer mechanisms that have to be taken into account can be divided into solid-solid conduction between the tip and the sample in contact; liquid conduction (if certain humidity which takes place in the real measurements and formed liquid meniscus around the tip is present) and gas conduction (when heat is transferred through the surrounding atmosphere from the tip to sample). One example of these models, where the surrounding gas around the tip and the sample is taken into account, shows how these effects can distort the thermal signal and diminish the spatial resolution [25]. Therefore, experiments performed in vacuum were carried out. Nowadays, SThM has evolved and is currently applied to many different micro- and nanosystems. Thermal models to better understand the thermal transport and heat transfer mechanisms at the micro- and nanoscale and how these influence the measurements, along with novel calibration techniques to achieve better results, have been developed [26, 27]. These have also contributed to a better understanding of the technique and to obtain quantitative measurements. Another method proposed in 2008 to perform measurements in ambient condition, was proposed using a double scan technique [28]. Most of these contributions can be separated in applications to 1D structures, such as nanowires [29, 30] or carbon nanotubes [31, 32], 3D materials [33], thin films [34] (which are the objective of the present chapter), and in the last years, the SThM technique has also been successfully applied to the study of the emerging field of 2D materials [35].
\nAs it was aforementioned, in this chapter, we will explore the characterization of the thermal conductivity of thin films by SThM. Firstly, we will discuss the different operational modes of the probe along with an overview of different kinds of probes that can be used, their applications, and their limitations. Then, we will focus on two different types of heating mechanisms (AC and DC) implemented in thermistor probes, along with their theoretical models. Finally, we will review some experimental results, most of them from our own group, devoted to extract the thermal conductivity from the thermal response of SThM measurements in thermoelectric thin films. For thermoelectric applications, where temperature gradients are converted into electricity by the thermoelectric (TE) effect, the accurate characterization of the actual thermal conductivity of thin films is fundamental to optimize their performance. The most efficient TE materials are those which exhibit both high Seebeck coefficient and electrical conductivity along with reduced thermal conductivity. One way of reducing the thermal conductivity of a bulk material without affecting the transport properties is through reducing its dimensionality [36], such as preparing thin films. This thermal conductivity reduction has been reported for several materials, such as SiGe [37, 38, 39] Cu2Se [40] and Ag2Se [41] films, among others.
\nAs it was mentioned in the Introduction, once the SThM probe approaches the surface of the sample and heat starts to be transferred, there are two different modes of operation: passive or active. On the one hand, in the passive mode, the temperature of the probe is monitored while scanning the surface, thanks to a constant current that passes through it. This provides a way to detect changes in the temperature of the probe, but this current must be also small enough to avoid self-heating. This measurement mode was implemented by Majumdar in 1993 [11]. On the other hand, the active mode implies that high currents pass through the probe, in order to be heated by Joule effect. Then, part of this heat will flow to the sample and this heat flow will depend on the thermal conductivity of the sample and the temperature difference. Therefore, in this mode, the probe is behaving as a heater. But, it also acts as a thermometer, given that the temperature is monitored by measuring the voltage of the probe, and this can be related to the thermal conductivity of the sample. This active mode can also be divided into two different operation modes: operation at constant current or at constant temperature [12]. In the first case, the active probe is connected to a constant current and the heat flux between the probe and the sample is detected by changes in the resistance of the probe. In the second case, the active probe works at a constant temperature by changing the applied voltage in the probe to keep its electrical resistance constant. This last operation mode is known as active mode at a constant temperature. This mode has the fastest time response to reach local thermal equilibrium to operate.
\nThese measurements can be done with a variety of probes. We will introduce two of the most used kinds of probes: thermoelectric and thermistor. At the end of the section, the main characteristics of those probes will be shown in Table 1.
\nSpecifications | \nSThM probes | \n|||
---|---|---|---|---|
Thermoelectric | \nThermoresistive | \nSemiconductor | \n||
Thermocouple junction | \nThermocouple Wollaston wire probe | \nThermistor Pd/ Si3N4 probe | \nDoped silicon resistor probes | \n|
Passive | \nAt constant temperature | \n\n | \n | \n |
Active | \n\n | At constant current | \nAt constant current | \nAt constant current | \n
\n | Thermal conductivity, TE properties | \nThermal conductivity, Seebeck | \nThermal conductivity, Seebeck | \nNanolithography, nano-LTA, glass transition, melting temperature | \n
Cantilever materials | \nSi3N4 SiO2, Si | \nAg shell Al mirror | \nSi3N4 NiCr limiters Au pads | \nSilicon (highly doped) | \n
Spring Constant (Nm−1) | \n0.35 | \n5 | \n0.5 | \n1 | \n
Tip materials | \nAu, Cr | \nPt90/Rd10 | \nPd | \nSilicon low doped | \n
Tip height (\n | \n0.1 | \n100 | \n10 | \n\n |
Tip radius (\n | \n0.065–0.1 | \n\n\n | \n<0.1 | \n0.01–0.02 | \n
Nominal electrical resistance of the probe (\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n
Max. temperature (\n | \n600–800 | \n100 | \n160 | \n1000 | \n
Temperature coefficient resistance (K−1) | \n\n | 0.00165 | \n0.0012 | \n\n |
Thermal cutoff frequency 2 fc (Hz) | \n\n | 250 | \n2750 | \n\n |
Thermal lateral resolution (\n | \n\n | 1–2 | \n0.060–0.100 | \n\n |
Topographic lateral resolution (\n | \n<0.03 | \n<1 | \n0.030–0.060 | \n0.1 | \n
Summary of the properties of the different SThM probes mentioned in the text.
The first type of thermal probe developed was a thermocouple placed at the end of a tungsten STM tip, used by Williams [6] and Majumdar [11], to study temperatures of nonconductive surfaces. These probes are being improved, and their properties are still under study. For instance, to know if the contribution of radiative heat transfer between a SiO2-coated TE tip and the SiNx-coated sample is negligible when compared with conductive heat transported by solid contact [42]. In general, thermoelectric (TE) probes have a nanoscale thermocouple junction at the tip. Further experimental and theoretical efforts were focused in obtaining thermal images in the sub-100 nm of spatial resolution using a thin-film thermocouple junction at the tip end [43]. New design and batch-fabricated TE probes were proposed in [44], to simultaneously improve the thermal sensitivity, the tip radius, and the thermal time constant (see the scheme in Table 2). In general, these tips can be used in active or passive mode, and are quite adequate to study heat dissipation, temperature distribution, and thermoelectric properties of both materials and devices. As far as the geometry and materials of these kinds of tips, the cone is around 8 μm in height and 8 μm in width at the base, and it has to be made of a low-thermal-conductivity material, such as silicon dioxide (SiO2), to avoid heat losses from the TE junction to the cantilever. Then, the thermocouple junction films located at end of the tip are usually around 200 nm and the metals used for the junction are typically gold and chromium, isolated from each other along the probe with a Si3N4 film (see Figure 1).
\nSummary of advantages and disadvantages of the different thermistor types of probes discussed in this section.
With these kinds of probes, apart from studying the heat transport in different samples, other thermal properties, such as the interfacial thermal resistance, can be determined with the appropriate experimental setup and theoretical models. For instance, in Refs. [45, 46], these probes were used in active mode and through the measurement of the 2ɷ signal, they obtained thermoelectric properties of the samples. To this end, they heated the sample with a Peltier element, while the TE probe was Joule heating and scanning the sample. The analysis of the recorded signal was made by a steady periodic electrothermal model to obtain the thermoelectric parameters of the sample. Some disadvantages that these probes present is a low thermal sensitivity, which makes the temperature profiles obtained with them rather noisy. The resolution can be improved in vacuum, but working in these conditions can affect the temperature gradient. Also, it is necessary to include a circuit and a modified setup for some measurements, which complicates both the experimental implementation and the theoretical models needed to extract the properties [44].
\n(a) SEM image with the top view of TE probe. (b) Side view of the probe. (c and d) SEM images at different magnifications of the tip. In (c), the detail of the thermocouple junction can be seen; (a), (b), and (c) are taken from
Thermistor probes were introduced by Pylkki et al. [12] in 1994. These probes have a thermistor element, which can be a metallic thin film, a wire, or a highly doped semiconductor. This thermistor varies its resistance with temperature. Therefore, the temperature of the probe can be monitored by recording its change in electrical resistance. Since then, the field of thermistor probes has evolved, and here, we will introduce different types, which have been commercially implemented: Wollaston wire, microfabricated (Pd/SiN), and highly doped semiconductor probes. A summary of the advantages and disadvantages of each of the thermistor probes is shown in Table 2.
\nThe Wollaston probe was designed and implemented for SThM measurements in 1994 [12], and it was commercialized by Bruker®, although they are not commercially available anymore. This commercial probe was used in our group in different works, [33, 37, 48], which will be discussed in Section 4.1. It consists of a 5 μm in diameter core wire alloy of platinum-rhodium (Pt90/Rd10) with a silver shell of 75 μm. Around 200 μm of the Pt90/Rd10 core is exposed by an electrochemical etching and bent into a V-shape (see Figure 2). This alloy of the core is the thermistor element, and thus sensitive to the heating, and therefore, the changes in the resistance of this filament are monitored during the scanning of the sample. A mirror for optical beam detection is stuck to the probe by means of an aluminum-coated tape, stacked across the arms of the cantilever, allowing detecting the cantilever deflection by an AFM system. With this kind of probes, for example, memory alloys based on structural transformation have been investigated, such as the studies on the thermal conductivity of NiTi microstructures through their phase transitions carried out by Chirtoc et al. [49]. Moreover, depending on the operation mode implemented during the experiment, not only thermal conductivity but also the Seebeck coefficient can be measured, as recently published in Refs. [33, 50], working in contact mode. Also, recent publications dealing with Wollaston probes are focused in the quantification of the thermal parameters by studying the theoretical heat transfer models in noncontact mode [51].
\nDifferent images of Wollaston wire probes used in our measurements, where the exposed Pt90/Rd10 core bent in a V-shape can be clearly seen, with increasing magnifications from an optical microscope image in (a) with a complete view of the probe with the mirror and the silver legs to (b), where a scanning electron microscope (SEM) detail of the exposed core with a V-shape can be seen. SEM images (c) and (d) show a Wollaston probe after several uses, presenting dust attached to the wire in (c) and a distorted shape in (d).
Among the advantages to use a Wollaston probe for thermal thin film characterization, it is worth mentioning that they have been used for a long time, and consequently, they are quite well known and they have been extensively used for heat transfer investigation. There are several contributions that analyze theoretically and analytically their behavior. The calibration processes and data reduction can be simplified as it was done in [33] for a scanning hot probe. Besides, these probes can be useful in case that spatial resolution of no more than a few microns is required, or if thermal and topographic images are not desired, since these probes can be easily implemented in a piezoelectric system, acting as thermometer and heater for different applications to perform thermal analysis with a simple experimental setup and fast data acquisition time.
\nNevertheless, the reproducibility and the repetition of the experiments can result complicated, given that not only these probes have bending problems of the exposed core, but also the V-shape can change after certain uses or number of scans (as it can be seen in Figure 2c). Another disadvantage is that, as far as we know, currently, there are no companies that commercialize these probes, and thus, the only way to use these probes for thermal experiments nowadays is to fabricate them in the laboratory.
\nThese types of probes are specially designed for contact mode. They use a thin metal film (of about 50 nm thick) as thermistor element. This film is located near the apex of the tip, and the cantilever is made of silicon dioxide (SiO2) or silicon nitride (Si3N4). The probe has two current limiters of nickel chromium and gold pads to perform the electrical connection. The tip height is usually around 10 μm to maximize the separation between cantilever and sample as a way to avoid heat losses by the cantilever-sample interaction. In the images of Figure 3, we can see a microfabricated Pd/Si3N4–commercialized by Bruker® and used in our group to perform thermal conductivity characterization of films, as it will be shown in Section 4.
\nDifferent scanning electron microscope (SEM) images of a microfabricated Pd/Si3N4–commercialized by Bruker® used in our measurements, with increasing magnifications from (a) to (b). Images (c) and (d) show probes where the Pd film of the tip has been removed after electrical breakdown. The angle of the tip can also be clearly seen in (c).
One of the main advantages of using these types of probes is the high thermal and topographic resolution that can be achieved. Also, the cutoff frequency when the probe is heated in AC mode is higher in microfabricated probes than in Wollaston wire probes, as it was reported in [24]. In the same works, the authors highlighted that image acquisition time could be reduced from 1 h in the case of using a Wollaston probe to only 6 min when using a Pd/SiO2 probe, for an image of 256 × 256 points.
\nAmong the drawbacks that these probes have, one should mention that they are highly static sensitive, so it is not recommended to measure their electrical resistance with conventional resistance meters. Instead, a very careful management is recommended to avoid electrically breaking the probe. In Figure 3d, it is shown how the probe looks when the Pd film has been removed, which can occur due to its high static sensitivity. Another disadvantage, when compared with Wollaston wire probes, is the price, which comes from the fact that this is a microfabricated and highly specialized probe. Finally, it is worth mentioning that implementing a heat model for these kinds of probes is also an issue, apart from the calibration steps that have to be done in the probe prior to measure with them. In order to calibrate each probe, many geometrical parameters and material properties must be taken into account to fix the calibration curves, as it is shown in Ref. [29], for instance.
\nIn the case of these microfabricated probes, the most used semiconductor material is silicon, which are micromachined in a U-shape, that consists of a low doped platform, which will act as the resistive element (heater) and two highly doped silicon microlegs. Then, the tip is mounted on the resistive element, with a conical [52] or pyramidal [53] shape and curvature radius as low as 10 nm (achieving 100 nm in spatial resolution). The fabrication of these tips is based on microelectronics processes, and thus, batches of sharp probes can be fabricated (see Figure 4). These probes were first developed for high-speed nanoscale lithography applications and data-storage systems by IBM, but working in active mode, nanothermal analysis can be performed [54].
\nThe main advantages of these probes are, as it was mentioned before, is the high resolution that can be achieved, allowing even a three-dimensional analysis of nanoscale confinement of certain effects, such as phase transitions (which is not possible when using Wollaston probes, for instance) [53], serving as a highly localized heat source. Moreover, given that they can be produced with scalable fabrication methods, predictable and repeatable thermal parameters in all of them can be produced, along with an important cost reduction. Finally, another relevant benefit of these doped silicon probes is that they can be used in biological media, as in Ref. [55], where they were used to differentiate molecules based on their different heat conductivities.
\nAs far as disadvantages when using these probes for thermal measurements, one has to take into account that they are mainly used for nanolithography and data storage, given that they can deliver up to 1000°C. This reverts to a difficult analysis of the experimental data obtained, given the high thermal contact resistances at the end of the tip, as shown when measuring thin films of polystyrene [53]. Another difficulty for their use in thermal conductivity characterization is that the variation of their electrical resistance cannot be completely described by a linear relation with temperature [56], as it could be done in the previous cases, which further complicates the qualitative measurements.
\nScanning electron microscope images of microfabricated semiconductor probes, showing different magnifications in the case of (a) pyramidal and (b), (c) conical SEM image in (d) is a part of a whole array of microfabricated cantilevers; (a) is taken from Ref. [
From now on, we are going to focus on SThM measurements where the local temperature and thermal conductivity of the films are extracted using a thermistor probe. In such a way, while scanning the surface of the sample, the probe can be used as a nanoscale thermometer, as in passive mode operation. But as we saw in Section 2, the probe, if used in active mode, behaves not only as a thermometer but also as a heater. Therefore, if one measures the voltage drop across the probe while a known current passes through it, or if a Wheatstone bridge is used to detect the changes in the resistance of the probe, the actual temperature of the probe can be known, after certain calibration steps. Both of these modes, active or passive, allow the performance of measurements heating the probe with a direct (DC) or an alternate current (AC). The use of an AC current has the advantage of a high signal-to-noise ratio, mainly when combined with lock-in detection, and it also allows the use of the 3
Experimental SThM measurements performed in DC mode can be treated by analytical models to extract the thermal transport properties of the samples. In the case of measuring thin films, several parameters such as the thickness of the film and the influence of the substrate must be taken into account, apart from other general parameters of the measurement system, such as the geometry of the probe, the heat transfer exchange radius, among others. In order to theoretically model the experimental setup when the probe is heated in DC mode, one can simulate the tip by a fin of length
where the index \n
In order to obtain an analytical solution for Eq. (1), one has to assume certain boundary conditions, such as keeping the end of the probe at ambient temperature. Also, the geometric characteristics of the probe have to be known and uniform temperature distribution at the tip region has to be assumed. Then, an expression for the average temperature of the probe can be obtained as:
where \n
where \n
Schemes of the thermal resistance network and thermal interaction between the probe and the sample.
where \n
It is worth mentioning that AC heating is more workable with microfabricated probes, due to their smaller thermal mass and higher cutoff frequency when compared with Wollaston probes [59]. Then, in this case, if the thermistor probe is heated with an AC signal, the resulting temperature is a contribution of both a DC and AC profiles. If we define the AC current as \n
where the \n
where the index \n
where
As it has been seen along this chapter, the SThM technique is quite suitable for the measurement of thermal properties of thin films. In the literature, one can find many examples, such as the work from Oesterschulze et al. in 1996 [61], where they used a combination of a photothermal SThM and STM setup. In such a way, they obtained at the same time the topography, the DC image of the temperature, the AC temperature amplitude, and the phase image of thin polycrystalline diamond films. Thanks to the thermal images, some features that were not visible in the topographical image could be studied. In this case, the thermovoltage map was correlated with the single crystallites, where thermovoltage was constant. On the side planes, the decreasing of thermovoltage was related to the laminar structures parallel to the edges of the top plane. More recent works on thin film characterization by SThM [62] deal with the correlation of the thermal properties of BaTiO3 thin films with their morphology. In order to give further examples of the application of the SThM technique, we will discuss next some examples of measurements performed in thermoelectric thin films from our group.
\nTo perform measurements with a Wollaston probe in thin films, a circuit as the one shown in Figure 6a was implemented. Prior to the measurement, a thorough calibration of the system was necessary. This calibration consists of measuring three different samples of known thermal conductivity to determine the thermal exchange radius (
(a) Electrical circuit used for the measurement with the Wollaston probe (reproduced from [
In order to enhance the thermal image resolution to explore different thermoelectric thin films and study their nanostructure, it was necessary to change the probes from Wollaston to microfabricated probes. In this case, the electrical circuit used, which can be seen in Figure 7a, consists of a home-made Wheatstone bridge, which will be used to detect the resistance changes of the probe, connected to a lock-in amplifier from Zurich Instruments®. Finally, the lock-in is connected with an AFM from Nanotec Electronica®, in which the tip is mounted. In this way, topographic and thermal images of the sample are simultaneously obtained. The thermal conductivity was obtained using an active mode at constant current and under ambient conditions. To obtain the geometrical parameters of the probe and its thermal response, it is necessary to perform a prior calibration both in ambient conditions and in high vacuum (10-5 mbar), as it was mentioned in Section 2.2.2 [29]. In order to analyze the thermal response of the probe in out-of-contact mode, one varies the applied frequency while detecting the 3ω voltage, both in vacuum and in atmospheric conditions, obtaining a graph such as that shown in Figure 7b. This has to be made with special care to avoid any electrical breakdown of the tip. These data have to be fixed with a theoretical curve, which takes into account the geometrical parameters of the probe (length, thickness of the Pd and the SiNx, the convective coefficient, electrical resistance, temperature coefficient resistance, etc.). With these geometrical parameters fixed, a different model is used to determine the equivalent thermal response of the tip,
(a) Scheme of the experimental setup and electrical circuit with the Wheatstone bridge, (b) experimental data and model adjustment of the measurements of the 3ɷ response of the probe versus thermal frequency at atmospheric conditions (from [
This experimental setup was successfully implemented to obtain thermal images of different thermoelectric films and to determine their thermal conductivity. For instance, in the work of Perez-Taborda et al., a novel fabrication method to obtain thin films Cu2Se with high control over the stoichiometry was achieved [40]. In this case, the thermal conductivity at room temperature under ambient conditions obtained via SThM measurements, arouse a value as low as 0.8 ± 0.1 W/m·K, which results in a TE figure of merit of 0.4. A detail on these measurements can be found in Figure 8, where the topographic and thermal images can be seen. Apart from the good resolution of the images, the most important feature shown in these images is that the V3ω voltage is not influenced by the artifacts or topographic effects. This can be seen in Figure 7c and f when numbers 1 and 2 located inside of the images are compared. The V3ω voltage is quite homogeneous along the surface of the film, and it is not much influenced by the topographical height. It is also worth mentioning that the highest values in V3ω are the regions with the lowest thermal conductivity.
\n(a and b) Topography images at two different scales, and (c) shows a profile along the blue line in (b); (d) and (e) show the thermal images at the same scale than (a) and (b); and (f) shows the corresponding profile along the blue line in (e). Note that numbers 1 and 2 in these profiles indicate the same lateral displacement position for topography and V3ω (images (a) and (d) are adapted from Ref. [
Microfabricated probes were also used for the measurement of Ag2Se films, which presented a different morphology of bigger grains than in the previous case, which does not affect the thermal conductivity (see Figure 9). These films, of around 700 nm in thickness, presented in [41], had a highly reduced thermal conductivity (0.64 ± 0.1 W/m·K) when compared to the same material in bulk (reported as 1.5 W/m·K [63]). In this case, this reduction in the thermal conductivity, along with the good measured transport properties, arouses in a thin film with a TE Figure of Merit (
(a) SEM, (b) topographical, and (c) thermal map images obtained with SThM using a Pd/Si3N4 microfabricated probe (from [
The thermal conductivity characterization and local temperature measurements at the nanoscale of thin films are of the utmost importance in a great number of fields, such as in electronics, where heat management is vital for the final efficiency of the devices, solar cells, coatings, etc. Among those fields, thermoelectricity stands out, given that the reduction in the thermal conductivity due to nanostructuration is one of the main objectives nowadays to increase the thermoelectric performance of the materials.
\nAlong this chapter, we have presented the SThM method applied to the measurement of thermal properties of thin films. The main advantages of this method are the high resolution (in the nanometer scale), the possibility to simultaneously obtain the topography and the thermal image of the surface, and, from the experimental point of view, the sample preparation process is easily compared with other thermal characterization techniques. The SThM technique was first implemented in an AFM in 1993, and since then a great deal of effort has been devoted to understanding in depth both the heat transfer at the nanoscale and the phenomena that have to be taken into account in these kinds of measurements. After a review of the historical advances related to the development of the SThM, experimental details about the operational modes and different kinds of probes were discussed. Then, the theories behind the heating models involved in a certain type of probes were briefly introduced. At the end of the chapter, results obtained in our group on the thermal conductivity of thermoelectric thin films performed with SThM were shown, demonstrating the suitability of this technique for these kinds of measurements.
\nOne of the most appealing future directions based on these techniques would be the use of multipurpose probes to obtain, at the nanoscale, simultaneous information about electrical, thermal, chemical and mechanical properties, among others. The main challenge would then be the understanding of the different transport phenomena at the nanoscale, and how to physically represent the different interactions between the probes and the samples. Therefore, the development of more complex models, along with the evolution of micro- and nanofabrication techniques, opens the door to a new blooming of methods based on SThM for a full characterization of thin film properties at the nanoscale.
\nThe authors acknowledge the financial support of the Intramural INFANTE, and MAT2017-86450-C4-3-R, as well as the service from the MiNa Laboratory at IMN, and funding from CM (project SpaceTec, S2013/ICE2822), MINECO (project CSIC13-4E-1794), and EU (FEDER, FSE). O.C.C. acknowledges the funding of the Ramón y Cajal program (MINECO).
\nThe authors declare no conflict of interest.
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"6",type:"subseries",title:"Viral Infectious Diseases",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11402,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. 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Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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