\r\n\tThis book will address the various modern, technical, and practical aspects of smart technology for capturing solar radiation and converting it into different forms of energy, as well as enabling it for renewables integration in energy generation and transformation, built environment, transportation, buildings, and agriculture.
\r\n\r\n\tThe book will cover the most recent developments, innovations and applications concerning the following topics:
\r\n\t• Solar radiation – Smart and enabling technologies for measurement, modelling, and forecasting
\r\n\tHigh-resolution measurement sensor and instrument technology (Pyranometers, Albedometers, Pyrheliometers, UV Radiometers, Sun Trackers, Spectroradiometer, Pyrgeometers, etc.), Artificial intelligence techniques for modelling and forecasting of solar radiation, Solar Irradiance forecast with satellite data, Solar potential analysis, Short-term forecasting of photovoltaic power and solar irradiance prediction with sky imagers.
\r\n\t• Renewable energy integration – Smart solutions for integration of RE in distributed generation, energy storage, and demand-side management.
\r\n\tIntegrated Photovoltaics: Smart technology for vehicle-integrated PV, Building Integrated PV, Agrivoltaics, Road-Integrated PV, Floating PV, Product-integrated PV.
\r\n\tRenewable Energy Applications in Built Environment and mobility: Solar cars, solar-powered electric charging stations, passive solar systems, solar heating, and cooling systems, building-integrated vegetation, multifunctional solar systems, solar pumps, solar lighting, solar shading, Natural lighting, Solar dryer, Greenhouse.
The human body harbors a plethora of mineral compounds that form the lifeline of our multifaceted biological system [1, 2]. To illustrate, major and minor elements play a critical role in metabolic pathways and physiological processes of the human body. However, when toxic elements or other xenobiotic compounds from the occupational or natural environment enter the body, elemental dyshomeostasis ensues that adversely affects the aforementioned processes. Poor nutrition is another contributing factor to elemental dyshomeostasis that results in a modified metabolism.
\nBesides its effect on metabolic processes, elemental dyshomeostasis in the body may also indirectly accelerate the germination of diseases such as neurological disorders and cancers that in turn may indirectly alter metabolic processes and elemental levels within tissues. A growing number of studies now highlight the complex association between elemental dyshomeostasis and biological disorders [3, 4]. Several reports also highlight the importance of monitoring elemental levels as a measure to treat elemental imbalances and prevent the onset of disease or alternatively, as an outcome of disease [5]. Applying such disease intervention through biological tissue elemental screening is however complicated and requires a more in-depth analysis of the full elemental signature of human tissues in the pre- and postdisease stage.
\nElemental profiling of biological tissues now finds diverse applications in the fields of biomedicine, pharmacology, toxicology, and forensic science [6, 7, 8, 9]. Of the biological tissues used in elemental profiling studies, hair is gaining increasing popularity for quantitative profiling of elements in the body. Since the elemental content in human hair fibers is generally less than 1%, accurate and sensitive analytical techniques are a necessity for studies focused on quantitative elemental profiling in hair fibers [10].
\nStudies related to hair elemental screening has mostly relied on conventional analytical techniques such as atomic absorption spectroscopy, inductively coupled plasma mass spectrometry, and inductively coupled plasma atomic emission spectrometry [11, 12]. Sample preparation for these aforementioned techniques presents a major pitfall in that elements may be lost or contaminants introduced during chemical processing of samples. A proposed extraction method may also yield high recoveries for some elements and low recoveries for others [13]. In essence, sample processing for these techniques is destructive in that samples from various donors have to be pooled and chemically processed that effectively destroys historical and spatial information of elements preserved within the length of a single hair strand [14]. Besides sample preparation, the capabilities and limitations of the testing instrument also warrant careful scrutiny. For example, some techniques may only reveal the presence of specific elements due to the instability of the analyte under imperfect experimental conditions or the low sensitivity of the technique [15, 16].
\nOne of the most versatile and sensitive analytical techniques for elemental microanalysis of unprocessed biopsy tissues in a manifold of multidisciplinary fields fall under the umbrella of ion beam techniques [17, 18]. The continual development of the components of the beam setup such as the beam optics and scanning systems, as well as the detection and data acquisition devices, has now firmly placed ion beam techniques at the forefront of elemental analysis research in the biomedical and other fields involving hair elemental screening [19]. Besides ion beam techniques, synchrotron radiation techniques are also becoming increasingly popular in biomedical research related to hair elemental analysis.
\nThis chapter aims to provide an overview of why hair is a popular testing substrate for elemental screening, how elements are incorporated into hair, how to prepare hair for ion beam and synchrotron radiation analysis, and an overview of the versatile applications of ion beam and synchrotron radiation techniques in hair elemental profiling in biomedical studies.
\nHair is a metabolic end product that incorporates minerals from the blood supply into its keratinous matrix during the growth process [14, 20]. Over time, a temporal profile of normal or abnormal metabolic activity or alternatively, exposure to xenobiotics such as heavy metals is created. Depending on the length of the hair shaft, segmental analysis may then reveal a pattern of exposure that enables a retrospective screening of short term or chronic exposure to chemical compounds [14, 21]. Other unique characteristics of hair include its ability to store higher concentrations of minerals than blood or urine for a number of years [22]. Furthermore, mineral levels in hair do not fluctuate in response to changing physiological and/or environmental conditions such as in blood or urine [23]. Most importantly, hair samples from regions such as the scalp can be collected noninvasively and under close supervision, minimizing the risk of manipulation and cross-contamination, and is easy to handle, transport, and store [14].
\nHair has become a popular tool for screening and quantifying for example elemental changes within the body [14, 24]. Alternatively, hair testing may find important applications in clinical medicine such as to (1) determine medicinal or chronic doping, (2) confirm gestational drug use, or (3) assess exposure to toxins and pollutants in the workplace or environment [25, 26]. Hair analysis has also become popular in forensic science to (1) assess drug use history, (2) criminal liability of drug users, and (3) intentional or unintentional poisoning in postmortem toxicology [27, 28, 29]. Unfortunately though, there is a lack of reports describing the mineral profile of intact, unprocessed hair in its natural physical and chemical state [14]. Fundamental information on the spatial distribution of elements within hair tissues is also lacking, which is particularly important when distinguishing for example exposure to ingested xenobiotics originating from blood feeding the inner hair tissues or exposure to environmental pollutants that accumulate in the outer hair tissues. Furthermore, how elements and drugs are absorbed and incorporated into hair, either biogenically or diagenetically, are also still poorly understood. These unanswered questions may, however, be probed by techniques such as ion beam analysis and synchrotron radiation that allows quantitative elemental spatial data that may also assist in understanding hair elemental uptake mechanisms.
\nUnderstanding hair elemental uptake or incorporation mechanisms and the factors that may influence elemental levels in hair is crucial before correctly interpreting ion beam analysis and synchrotron radiation data [14]. Scientists have proposed three models explaining elemental uptake in hair [30]. The first model proposes that elements may either actively or passively diffuse into the hair shaft from the bloodstream feeding the dermal papilla cells. The second model proposes that elements may diffuse from sweat or other excretions into the hair shaft. Alternatively, powders and vapors may also diffuse into the hair shaft, as proposed by the third model.
\nBesides the aforementioned routes of entry, the incorporation of elements and their levels in hair may be significantly influenced by a range of other variables. These may include the dose of the chemical exposed to and the origin of the chemical [31]. Hair is often treated with a range of cosmetics such as mineral-based dyes, paints, and bleach for attractive appeal, while various shampoos such as antidandruff formulations that contain zinc and selenium are also frequently used for hygiene purposes [14, 32]. When hair is wetted before applying these formulations, the hair fiber swells and the cuticle cells lift [32], causing the hair fiber to be more permeable to cosmetic agents that are known to contain a variety of chemicals as well as tap water that may contain calcium and lead from plumbing. Bleaching may further increase the permeability of hair in that it destroys hair disulfide bonds that cause hair to be more vulnerable to aqueous solutions containing a variety of chemicals.
\nOther than cosmetic agents and washing that contributes to endogenous hair elemental levels, heavy metals deposited on the hair surface from atmospheric dust and pollution may also contribute to both exogenous and endogenous hair elemental levels [14, 33]. Interestingly, it has been shown in miners that particulates from mined metals may be deposited on the hair surface [34]. The surface contains distinct regions of varying chemical composition and is a unique site with varying binding affinities for different metals [31, 35]. These binding affinities may, however, be affected by hair acidity and hair cosmetic treatments that add negatively and positively charged ionizable groups to hair. Binding of metals to hair may also alternatively be influenced by the levels of eu- and pheomelanin polyanionic polymers. These compounds have been shown to bind metal cations in vivo or in vitro via electrostatic forces [14, 35].
\nOnce elements are incorporated into hair, various other factors may affect their levels in hair. UV exposure, aging, nutritional deficiencies, morbidity, medication use, and acute metal poisoning has been described to cause natural deterioration and hair structural changes that affect the ability of hair to retain elements [14, 36, 37]. Specifically in disease, the levels of elements in the body may not be optimal and indirectly affect hair growth and hence hair structure. Besides the aforementioned variables, gender and age, ethnicity, and genetic polymorphisms may also influence the structure of hair and hence its ability to retain elements [14, 38, 39, 40]. For example with ethnicity, the structure, shape, and melanin levels of hair from different races may affect permeability and hence elemental levels within hair [14, 41]. Ethnicity may also strongly link with cultural habits related to washing and hair treatment regimens, as well as dietary differences that indirectly affect hair elemental levels [42].
\nBefore hair samples are sourced, it is important to first obtain ethical clearance for working with human tissues. Another important consideration is to obtain informed consent from participants who will be donating their hair. Ethical approval from an institutional ethical board is a necessity. Research institutions usually provide comprehensive information on application and approval processes as well as submission deadlines on their webpages related to the ethical clearance of studies. Ethical clearance of studies involving human tissue may take up to 1 month, depending on the institutional review times. Alternatively, one may also request an expedited review in the cover letter accompanying the submission, since research involving human hair constitutes minimal risk research.
\nWhen sampling human hair, it is important to consider the location of sampling. Although scalp hair may be exposed to external contaminants, scalp hair is often the preferred sampling choice [43]. Pubic hair may present the ideal alternative to scalp hair as it is less exposed to contaminants [42]. However, pubic hair differs in morphological and structural properties from scalp hair that may impact on elemental uptake mechanisms. Furthermore, there is a large possibility of participants manipulating samples when not supervised during sampling.
\nThe hair should be sampled as close to the skin as possible with stainless steel or Teflon-coated scissors. Hair may also be plucked so as to extract the hair bulb that may be less exposed to contaminations. Furthermore, the hair bulb is the most active metabolic area of hair and may be particularly interesting to study [44]. For retrospective analyses, it is recommended that long hair be sampled as segmental analyses may reveal a pattern of exposure that enables a retrospective screening of short-term or chronic exposure to chemicals [45, 46]. The hair should not be handled with plastic gloves as polydimethylsiloxane contaminants may be transferred to the hair. These compounds negatively influence data retrieved using certain analytical applications such as scanning ion mass spectrometry (SIMS) [47]. Once the hair samples have been properly processed, it may be stored in paper envelopes.
\nTo produce credible results, hair that is free of surface contaminants should be analyzed. To eliminate surface contaminants such as particulates from pollution, smoking, chemical powders, and metals from mining practices, most studies wash their hair samples [14]. With that said, the question of how specific external contaminants contribute to endogenous content still remains to be more rigorously investigated. Furthermore, if certain external contaminants were to become embedded in hair, distinguishing contribution from endogenous versus exogenous elements then becomes very challenging, rendering washing of hair in essence a negligible step. Nevertheless, specific fields such as drug analysis for forensic purposes place strict emphasis on hair washing protocols as drugs in the form of powder or vapor has been shown to contaminate hair and result in false positives [48]. Alternatively, in pollution or toxicology studies, washing hair samples may simply not be necessary since determining the kind of matter deposited on hair and possibly entering the body is important.
\nA multitude of washing methods has been described in the literature, of which the most popular is described below [14]. The most popular of these methods include washing hair in an ultrasonic bath with acetone, deionized water, and 0.5% Triton X-100 solution. This process is followed by washing with ultrapure water and air drying. The International Atomic and Energy Agency, however, proposes washing hair with a nonpolar solvent such as double-distilled acetone followed by washings in a polar solvent such as deionized water and acetone. Each washing step should be performed for 10 minutes. Authors may also adapt their hair washing protocol to be most suitable and efficient for their specific type of analysis.
\nThere is, however, a number of concerns related to hair washing protocols. First, no standard washing procedure is currently available in the literature that unknowingly introduces variation in hair elemental data and that has been confirmed after testing different washing protocols [49]. Second, authors may not always provide sufficient information on their washing protocol such as whether samples were sonicated and the specific solvents employed. Thirdly, insufficient washing methods may not remove surface contaminants, while washing methods that are too abrasive may cause damage to the hair sample and cause elements to either leach or diffuse into the hair, which often further complicates the assumption of elements either being of biogenic or diagenetic origin. Alternatively, no contamination may be present then representing [14]. In essence, a standard washing procedure that preserves internal elemental content and washes away external contaminants remains an urgent requirement.
\nBesides washing protocols for distinguishing between endogenous and exogenous hair elemental content, ion beam techniques have shown great promise for spatial distribution analysis of elements in hair tissues [14, 50]. When preparing hair for ion beam analysis, the hair may either be washed or left untreated. However, exposing the internal hair tissues is critical to assist with spatial distribution mapping of tissues and for interpretation of elemental maps. Longitudinal sectioning of hair may be employed to expose the internal tissues of the hair that facilitates distinguishing elements present at the borders of the hair that may possibly link to contamination or alternatively, biogenic elements occurring in the hair medulla [51]. For this purpose, the hair can be sectioned using a stainless steel metal plate (60 × 110 mm) manufactured with 5–mm-wide grooves of depths ranging between 20 and 80 μm [52]. A single hair is laid in a groove of fitting depth, secured, and sectioned longitudinally with a stainless steel razor blade (\nFigure 1\n). The sectioned hair may be mounted on a silicon wafer with carbon tape (\nFigure 2\n) in the case of SIMS at MeV energies [53]. Alternatively, the hair may also be mounted intact in special holders, allowing analyses along the length of a hair. Longitudinal sections of hair are particularly useful for the retrospective assessment of exposure to chemicals.
\nLight micrograph of a longitudinally sectioned scalp hair fiber (unpublished data).
Longitudinally sectioned scalp hair strands secured on silicon wafers (S) with carbon tape (C). The incised surface should be positioned to face the primary ion beam.
Some studies also cross section hair and analyze these cross sections with an ion beam technique termed microproton-induced X-ray emission spectrometry [50]. Cross sectioning of hair tissues may be performed using cryosectioning [54] in which hair fibers are fixed to a small piece of adhesive tape, which is embedded in 2% carboxymethyl cellulose and flash frozen in liquid nitrogen for 2 minutes. The frozen specimens are subsequently sectioned using a cryostat set at a temperature of −20°C. Cryosections of approximately 5 μm thickness can be prepared using a cryostat microtome (\nFigure 3\n). Data from a cross section of hair may well complement data from a longitudinal section in that more information becomes available on the elemental distribution in an area of hair containing different hair tissues. Such analysis may also effectively aid in determining elements distributed at the root sheath or cuticle cells and medulla of the hair and hence distinguish external contaminants from biogenic elements.
\nLight micrograph of an animal hair fiber sectioned under cryoconditions (unpublished data).
The aforementioned sectioning techniques may only be relevant when screening small sample sizes. However, for population studies, it is more advisable to analyze hair samples from a large number of participants that have been homogenized and pelleted [55]. This approach, however, has several disadvantages. Sampling requires a high number of participants, retrospective analysis will not be possible, information from specific individuals is lost as hair samples are homogenized, and contaminants may be introduced during sample processing. Sampling processing involving bulk processing is, however, fairly simple and traditionally involves homogenizing the hair samples into a powder using the brittle fracture technique. Approximately 2 g of hair are homogenized in a Teflon container and ball, which has been cooled with liquid nitrogen for 3 minutes. The container containing the hair and Teflon ball is vibrated for 2 minutes at 3000 cycles per min using a “micro-dismembrator.” The longer the procedure is repeated, the finer the hair powder obtained. The fine powder should be carefully mixed, stored at room temperature, and pelleted before analysis. Graphite (1% pure reactor grade) may also be added to the mixture to reduce charging of samples. Homogeneity and uniformity of the sample are extremely important, particularly when using ion beam analysis techniques where the spot size of the beam is smaller than the sample to be irradiated.
\nHair analysis has to date mostly exhausted conventional techniques that require digestion and hence destruction of a relatively large amount of hair. Such bulk analyses destroy information on the localized concentrations of minerals in a tissue. Ion beam and synchrotron radiation techniques have proven to be a solution to this dilemma. Numerous publications now exist that demonstrate the versatility of ion beam and synchrotron radiation analysis to map the quantitative distribution of minerals in hair cross sections or show the longitudinal distribution of elements in hair tissues [56, 57].
\nThe unifying characteristics of these techniques include their sensitivity, selectivity, quantitative multielemental character, and speed of analysis [58]. Furthermore, depth profiling without physical sectioning is often possible with ion beam techniques, while the ion microprobe may allow μm or lower spatial resolution for diverse applications. Analysis of intact samples without any chemical processing or dissolution is also possible, whereas damage to analyzed samples may be minimal, allowing for downstream analyses with other techniques.
\nIon beam and synchrotron radiation methods are based on the interaction of nuclear particles with atomic nuclei. Chemical bonding information is, however, not available as the electronic shell of the atom does not contribute to the physical process. Chemical speciation information is also not available with certain ion beam techniques, although results are not affected by the chemical form of the element. Furthermore, only surface near regions may be analyzed in most cases because of the short range of ions in matter. Perhaps the most significant downside of these techniques is the expensive equipment required and the fact that access to nuclear analytical facilities and expertise may not be accessible in some developing regions of the world.
\nImportant considerations when performing nuclear analysis include the type of standard to use, the thickness of the sample, as well as the effect of irradiation on the sample [59]. The use of standards may vary depending on the type and aim of the study, while it is imperative to analyze relatively thin material (few nm to 10 μm) due to the energy loss of the charged particles. For irradiation effect, there are some detailed studies on whether analysis with ion beams lead to sample damage. To illustrate, in secondary ion mass spectrometry analysis at MeV energies (MeV-SIMS) and at low beam fluences—meaning the number of primary ions hitting the target area unit—the analysis should be nondestructive [60]. Over time, the yield of secondary molecules should also exponentially decrease as a function of beam fluence. The slope of this exponential fall is determined by the damage cross section, which explains the damage induced on the specimen surface by one primary ion. Experiments at the Jožef Stefan Institute in Slovenia utilizing a 5.8 MeV 35Cl6+ primary ion beam reported damage cross section values of approx. 2 nm2 for the amino acids arginine and leucine. A fluence of 1012 ions/cm2 is the commonly accepted static limit of MeV-SIMS corresponding to 3 hours of measurement that agrees to approximately 8% of the target surface undergoing chemical alteration due to ion-induced damage. Since hair sample measurements is normally 1 hour, the hair chemical environment and morphology should remain unchanged. Scanning electron micrograph images further confirmed that the morphology of the analyzed samples remained unaltered after 1 hour of measurement with MeV-SIMS [53]. With particle-induced X-ray emission, however, a clear change in the sample’s physical appearance can be noted when measuring for a longer time frame.
\nBesides sample damage, volatile analytes may also be lost during sample irradiation as a function of their thermal and radiation stability [61]. Adjusting the beam intensity and irradiation time may assist with alleviating this problem. Alternatively, another ion beam technique may be chosen to avoid this problem. For example, in-air proton-induced X-ray emission lends the advantage of performing measurements in air, resulting in negligible charging of the insulating targets, reduced radiation damage to the specimen due to the cooling effect of the air, and ultimately reduced loss of volatile elements [62]. Representative spectra obtained from a single hair fiber with in-air proton-induced X-ray emission is represented in \nFigure 4\n.
\nRepresentative in-air PIXE spectra from a single scalp hair, with the x-axis representing characteristic X-ray emission energy (KeV) and the y-axis representing X-ray emission intensity (counts) (unpublished data).
Another concern includes charge buildup on samples. For hair samples, charge buildup has been observed during bombardment with protons [55]. Many factors may influence this phenomenon, but most importantly, the thickness of the hair. Charge buildup and episodic discharging from samples lead to high background levels in the spectra and should be avoided at all cost. This may be achieved by blending thick targets with graphite or, alternatively, by coating thin samples with a layer of carbon or other appropriate conducting materials.
\nIn the subsequent paragraphs, the focus will be placed on specific ion beam and synchrotron radiation analytical methods used in hair analyses. It should be borne in mind that techniques such as neutron activation analysis allow analysis of an entire sample, while specific ion beam techniques allow analysis of only the surface of a sample.
\nNeutron activation analysis has been described as a versatile method with a low detection limit for sample analysis of over 60 elements (major and trace elements) [63]. Samples do not require chemical preparation in which volatile elements may be lost. In addition, laborious sample homogenization procedures are not required for when a large amount of samples representative of a population need to be analyzed. The technique further requires only a small amount of sample weighing from 1 μm to hundreds of grams. Samples to be analyzed may also vary in form and shape. However, this need to be taken into consideration as sample geometry may affect results and also influence the choice of standard. A schematic overview of the technique is provided in \nFigure 5\n.
\nSchematic overview of the basic principle of neutron activation analysis.
Instrumental neutron activation analysis is a popular analytical tool for the determination of elements in hair specifically for forensic applications [64]. Interestingly, instrumental neutron activation analysis has been applied in the forensic analysis of Napoleon’s hair [65]. Napoleon died at the age of 51 on 5 May 1821, with his death officially ascribed to stomach cancer. Extensive investigations exploiting hair analysis, however, tried to dispute the officially declared cause of death as stomach cancer. Radiochemical neutron activation analysis showed that Napoleon’s hair contained 10.38 ppm of arsenic. Longitudinal hair analysis to assess retrospective exposure to arsenic further showed that the arsenic was unevenly distributed along the hair length. Additional investigations with instrumental neutron activation analysis showed that Napoleon’s hair also contained mercury, and abnormal levels of chromium, antimony, and zinc that may have entered the body via food or medication. For example, Napoleon consumed a great deal of calomel that contains mercury to relieve constipation and thirst, while antimony was a component of tartar emetic, which was given to him shortly before his death as an agent to inhibit vomiting that would have expelled the poisons from his body.
\nDoubt, however, still exists whether the concentration of arsenic in Napoleon’s hair was of endogenous or exogenous origin as exogenous contaminants may also be evenly distributed along the length of the hair. Hair may absorb arsenic from external contaminants that include wallpaper, coal smoke, water, cosmetics, and preservatives. The absorbed arsenic from either endogenous origin appearing in the medulla or exogenous origin appearing at the hair surface regions may remain in the hair structure even after washing. The conundrum of differentiating exogenous from endogenous exposure in hair can perhaps be more clearly understood through the use of ion beam imaging techniques such as particle-induced X-ray emission.
\nIon beam imaging has become a very popular tool for understanding the distribution of minerals in biological tissues. For hair elemental screening, particle-induced X-ray emission has emerged as one of the most popular and powerful ion beam techniques allowing quantitative elemental mapping in tissues at micrometer or lower resolution that well complements data obtained using other techniques such as synchrotron radiation X-ray fluorescence (XRF). The only disadvantage of the technique is that not all countries have robust facilities hosting the technique.
\nThe technique falls under a broad family of X-ray emission techniques for the quantitative distribution mapping of low Z elements (20 < Z < 35 and 75 < Z < 85) [66]. Particle-induced X-ray emission is based on the irradiation of a sample with a high-energy ion beam (typically 1–2 MeV of H or He) that excites the inner electron shells of an atom, inducing characteristic X-rays to be emitted by de-excitation of the atom. As negligible overlapping of characteristic X-rays for different elements occurs as the energy of an emitted X-ray is characteristic for a target element, multielemental detection becomes possible. X-rays are measured by an energy-dispersive (for example Si[Li]) detector placed at an angle of 135° relative to the beam direction to minimize the Bremsstrahlung background. When correcting for absorption and X-ray yields, quantitative data for elements may be obtained at detection limits of orders of magnitude around 10 ppm for thick samples. Since the physical processes involved in the generation of X-rays are well studied, no standards are required for producing quantitative elemental imaging with proton-induced X-ray emission. Elemental imaging in samples is obtained by scanning the ion beam microprobe over the surface of the specimen with a penetration depth of up to 100 μm.
\nVariants of particle-induced X-ray emission such as microproton-induced X-ray emission and in-air proton-induced X-ray emission offer supplementary benefits. For example, microproton-induced X-ray emission offers the added advantage of spatially resolved multielemental analysis of micrometer resolution [66], while in-air proton-induced X-ray emission lends the added advantage of performing measurements in air resulting in negligible charging of the insulating targets, reduced radiation damage and loss of volatile elements due to the cooling effect of the air, and simple handling and changing of samples [62]. In essence, ion beam techniques such as proton-induced X-ray emission provide nondestructive, fully quantitative, and multielemental mapping at micrometer-scale or lower spatial resolution and μg/g-level sensitivity of samples that require minimal processing [67]. Examples of applications of ion beam imaging using particle-induced X-ray emission for hair research will be discussed in Section 6. It is also recommended that the readers familiarize themselves with the numerous literatures describing the experimental setup, analysis, and data processing for the technique.
\nAnother technique that may well complement particle-induced X-ray emission is time-of-flight SIMS. Particle-induced X-ray emission may be used to quantify the elemental fingerprint of intact human scalp hair fibers, whereas time-of-flight SIMS may give an indication of both organic and inorganic compounds present in longitudinally sectioned hair. Time-of-flight SIMS is currently one of the most sensitive surface analysis techniques for chemical mapping, providing micrometer or lower resolution for depth profiling of the first one or two surface monolayers in an intact sample [47]. In addition, it allows parallel analyses and imaging of multiple elements, isotopes, and molecules in complex samples without exhaustive sample preparation such as labeling to provide information on the spatial localization of organic and inorganic compounds [68]. The main drawback of the technique is, however, the inability to quantify secondary ions due to the effect of the chemical composition of the matrix on the yield of secondary ions, also commonly referred to as the matrix effect [69].
\nIn time-of-flight SIMS analysis, the sample is traditionally bombarded with ions in the energy range of 5–25 keV [68]. Recently, the technique has, however, also been tested with primary ions at MeV energies in a method termed MeV-SIMS [60, 70]. A schematic overview of the technique is provided in \nFigure 6\n. In MeV-SIMS, the interactions between primary ions and sample molecules are based on electronic energy loss, which creates a softer sputtering process and a 1000 times greater yield of larger and intact ionized molecules than conventional SIMS in the keV energy range. A pulse of specific primary ions at MeV energy—depending on the molecules of interest—is focused and rastered over the sample surface under ultra-high vacuum to generate position-dependent mass spectra [60, 70]. Various charged ions, also termed secondary ions, are released by the impact of the MeV primary ions with the sample surface. These secondary ions are of equal kinetic energy and enter a drift tube in which they are separated according to their mass-to-charge ratio. The masses of the secondary ions depend on the chemical composition of the sample scanned at each point, while the intensity of the secondary ion signal depends on the concentration of the particular compound in the area sampled as well as the ionization yield of the compound. The yield of secondary ions in turn depends on the incident angle, nature, and energy of the primary ion beam as well as the chemical properties of the target matrix.
\nSchematic overview of the basic principle of time-of-flight secondary ion mass spectrometry with high-energy (MeV) primary ions.
The technique allows (1) parallel counting of secondary ions matched with preselected masses obtained from the analyzed points and (2) simultaneous building of chemical images [47]. The technique further allows for mass spectra to be extracted from an image region and vice versa to display the distribution of a secondary ion within the tissue. Interestingly, the technique is also able to analyze isotopic composition of light elements in a matrix such as hair [53]. The reader is, however, strongly recommended to first familiarize themselves with the experimental setup and a range of available detectors, the mechanism involved in secondary ion formation and the effect of the matrix composition on yield, as well as data processing and multivariate statistics deployed in SIMS before tackling this robust and challenging technique.
\nWhen electrons travel near the speed of light and are forced to change direction by a magnetic field, electromagnetic radiation is emitted that is also commonly described as synchrotron radiation [58, 71]. Today, synchrotron radiation has become one of the most powerful methodological tools for understanding the properties of matter in various scientific fields. The distinctive properties of synchrotron light include its ability to provide an energy tunable source of X-rays that can be highly linear, circular, or elliptically polarized; have a high brightness and collimation; have a wide energy spectrum with energies ranging from infrared light to hard X-rays; and provide nanosecond long light pulses that permit time-resolved studies.
\nSynchrotron facilities are characterized by a storage ring from which synchrotron radiation is emitted in a forward direction in a narrow cone that is at a tangent to the electron’s orbit [71]. The width of this cone of electrons is affected by the speed of the electrons, which further affects the spectrum of the radiation, shifting it toward shorter wavelengths with increasing electron energy. The storage ring of so-called third-generation light sources is further equipped with magnetic insertion devices termed undulators and wigglers that are used to generate linear or circular polarized light by generating magnetic fields that drive electrons into an oscillating or spiral trajectory. These third-generation facilities may specialize in short-wavelength (hard X-rays), long-wavelength (soft X-rays), or vacuum-ultraviolet X-rays.
\nTo focus the X-rays on the sample at micro- or nanometer resolution, different types of X-ray optics are used at various synchrotron facilities [72]. Some of these systems such as the Kirkpatrick-Baez mirror system use two glancing-angle, bowl-shaped mirrors with a curve designed to demarcate the beam profile at a focal point. Other systems include refractive lenses or Fresnel zone plates. These optical systems permit hard X-rays to be focused to 30–150 nm spot sizes that are injected to the sample. Ideally, the energy of the X-ray beam should be selected over a specified energy range. X-ray spectra are recovered subsequent to step- or raster scanning of the sample in the x and y planes at 45° to the beam path. More than one detector may be used to capture the spectra and deliver data with the beam x,y coordinates for each incident beam point. Conventional detectors for various applications that are common include Si(Li) detectors, intrinsic Ge detectors, or silicon drift detectors.
\nProbably the most important aspect of the analysis is optimizing the absorption of the X-rays in the samples to be analyzed [72]. The absorption of different types of X-rays produced in a synchrotron is controlled by the photoelectric effect. However, absorption may also be influenced by the chemical environment of the sample and element oxidation state. When an X-ray penetrates a sample and its energy is lower than the binding energy of the core electrons in the element of significance, its atoms do not absorb the X-rays. When the energy of the incoming X-rays and the binding energy of the core level electrons of an element are equal, X-ray photons are absorbed. Photoelectrons are produced since the incident X-ray electrons excite the core electrons. For the atom to return to a ground state, an electron needs to fill the empty position of the ejected photoelectron. This transition energy or wavelength is released as fluorescence or as an Auger electron for lighter elements. The number or intensity of X-ray photons is positively correlated with atomic abundance and hence individual element quantities. This is however mostly true for thin samples in which self-absorption within the sample is negligible. The net X-ray intensities of the elemental makeup are obtained via spectral deconvolution methods.
\nThe absorption of X-rays into matter outlined above forms the backbone of a versatile synchrotron technique, X-ray absorption spectroscopy (XAS). The latter technique provides detailed information on elemental chemistry such as oxidation state and molecular geometry [72, 73]. Based on the energy region of interest, XAS can be further differentiated into X-ray absorption near-edge structure, extending from the pre-edge region to approximately 50 eV above the absorption edge and extended X-ray absorption fine structure (EXAFS), extending from about 50 to 1000 eV beyond the edge. Since electron transitions may occur from a partly bound and excited state in the pre-edge region, certain chemical features may become visible in this region. For EXAFS, the physical processes giving rise to the signal can be modeled by selected computer programs that allow accurate assessment of the identity of the surrounding atoms, bond distances, and coordination numbers.
\nAnother technique based on the absorption of X-rays in matter described above is XRF [72, 73]. XRF permits quantitative elemental mapping. The physics of the photon interaction with matter is also well understood, simplifying quantification of data. Although XRF is similar to proton-induced X-ray emission and scanning electron microscopy with energy dispersive X-ray spectroscopy, synchrotron XRF is more sensitivity due to a high photon flux, weak scattering, and the availability of a tunable beam. Currently, XRF is one of the most sensitive imaging techniques offering spatially resolved down to 100 nm and quantitative topographical maps for a range of elements at submicron resolution. Depth resolution, however, depends on the elements of interest and sample nature, although high penetration depths of up to 1000 μm is possible that allows imaging of thicker samples or in-situ experiments.
\nSince this section only summarizes the background to synchrotron radiation and applicable techniques for analysis of hair samples, it is recommended that the readers familiarize themselves with the numerous literature sources available on specific synchrotron radiation techniques applicable to their samples and familiarize themselves with the beamlines and experimental setup at a chosen synchrotron facility. The latter may include the type of source device (bending magnet, wiggler magnet, or undulator), mirrors used to deflect or focus the X-rays, monochromators used for sorting incoming X-ray energies, glitch avoidance (double diffractions occurring in monochromator cryst detectors), detectors, availability of true imaging microscopes, electronics, and most importantly, data collection and statistics. Furthermore, it is important to familiarize oneself with an optimal sample preparation and calibration methodology for a specific synchrotron technique, elements accessible with the technique, effect of external parameters such as temperature on sample analysis, and nonscientifically, the culture of the facility and its researchers. Most importantly, beamtime application procedures also warrant careful attention.
\nThe amount of literature on hair chemical and specifically elemental analysis has grown substantially in recent years and with the specific focus on elemental analysis, it has been shown that almost any macro, trace, and xenobiotic elements can be quantitatively measured and mapped in hair tissues. The predominant amount of work with ion beam and synchrotron analyses has, however, focused on analyzing the distribution and content of elements in the hair of diseased patients versus healthy controls or those exposed to environmental pollutants. In the subsequent sections, examples of selected studies that employed ion beam and synchrotron radiation analysis to link elemental content with morbidity and toxicology will be discussed.
\nThere is an alarming lack of fundamental studies describing the role of elements in the growth and physiology of hair or how elemental levels vary during the different growth stages of hair. Variation in elemental levels in hair at different stages of growth is also an important confounding variable in hair elemental research. The first researchers that tried to assess the quantitative elemental distribution in organ-cultured hair follicles during the anagen and catagen growth phases were from the Jožef Stefan Institute in Slovenia and ion microprobe facility ATOMKI in Debrecen [74]. Combined ion beam analysis exploiting proton-induced X-ray emission and scanning transmission ion microscopy were used to quantify elemental content in hair follicles during the catagen and anagen growth phases. The results showed that elemental concentrations were similar in selected parts of the hair follicle in both growth stages. However, the outer/inner root sheath keratinocyte layers of hair follicles in the catagen growth phase contained four times more calcium than the same regions in hair follicles in the anagen growth phase. These layers are known to express the receptor for capsaicin, TRPV1, which function as a calcium-permeable channel [75]. During the catagen growth phase of hair, an increase in the intracellular calcium concentration inhibits the proliferation of keratinocytes that triggers the induction of apoptosis [76]. In summary, this study showed the promise of ion beam techniques such as proton-induced X-ray emission and scanning transmission ion microscopy to improve our understanding of changes in elemental levels during hair growth.
\nThe deleterious effect of environmental pollutants such as lead on human health cannot be over emphasized [77]. The outcomes of lead exposure in children are particularly concerning due to its irreversible effects on one of the most sensitive organs to lead exposure, the developing brain [78]. In particular, children exposed to lead may have cognitive and behavioral effects that persist into adulthood [79]. To assess daily lead absorption during the prenatal phase, the longitudinal distribution of lead in fetal and parental hair was studied using synchrotron radiation micro-XRF [80]. The technique proved very successful in mapping lead along a longitudinal length that reflected a retrospective profile of lead exposure and absorption during the prenatal phase.
\nHair elemental profiles may also find application as risk factors for disease. For example, intraindividual variations of 32 hair elemental levels as epidemiological risk factors for atopic dermatitis in infants were studied using particle-induced X-ray emission combined with rigorous regression statistics [57]. Hair samples were retrieved 1 month after birth and also at 10 months after birth with the onset of atopic dermatitis. The results showed that selenium and strontium could be used as explanatory variables in a regression model for atopic dermatitis. However, large intraindividual variations for selenium and strontium could affect the regression coefficients for strontium and selenium. Particle-induced X-ray emission was specifically employed in this study to understand intraindividual variations for selenium and strontium to correct for intraindividual variations in the previously described regression model. Such type of approach combining analytical techniques with statistical models is particularly important in promoting the application of hair elemental data in epidemiological research.
\nTrace elements have also been shown to play an important role in psychiatric diseases. A study using proton-induced X-ray emission was conducted to assess the trace elements in the scalp hair of patients with alcohol-induced psychosis [81]. The results showed that iron and copper levels were higher in patients with alcohol-induced psychosis, whereas the concentrations of manganese and zinc were lower, compared to healthy controls.
\nThe same approach was applied to identify and quantify elements in the scalp hair of patients with bipolar disorder based on gender [82]. For males, the concentration of copper was higher in bipolar patients compared to controls, whereas the concentrations of manganese, iron, zinc, and selenium were lower in bipolar patients of both genders compared to healthy controls. The same was observed in females, except that instead of manganese, nickel was higher in bipolar patients of both genders than controls. Furthermore, the Cu/Zn ratio was found to be higher in bipolar patients of both genders. This is not surprising as it is known that elemental dyshomeostasis triggers the formation of free radicals that may in turn affect neurotransmitter activity that plays an important role in psychiatric disorders [83]. However, treatment may also affect elemental levels in psychiatric patients, emphasizing the importance of assessing elemental levels before and after treatment [84].
\nBreast cancer is a devastating cancer affecting the lives of many women and men around the world. Interestingly, hair samples have been used to assess the risk of breast cancer [85]. With XRF and X-ray diffraction techniques, it was shown that not only elemental levels but also hair structure differ between healthy controls and those with breast cancer [86]. More specifically, the data revealed that trace element levels were higher in healthy controls than in breast cancer patients and that wavelength of XRF presented with a 96% sensitivity compared to a 77% sensitivity for mammography, the gold standard for breast cancer s
Besides breast cancer, the effect of radiation therapy on hair trace elemental concentrations in cervical cancer patients has also been investigated with ion beam analysis; in this case, proton-induced X-ray emission [87]. Testing was done before and during radiation therapy. The concentrations of chlorine, potassium, calcium, titanium, chromium, manganese, iron, nickel, and zinc were lower and copper higher before irradiation. It was also shown that the concentration of specific elements varied during the course of radiation therapy, indicating a possible effect of this type of cancer therapy on elemental levels in the body.
\nElemental analysis of hair samples also now finds important applications in the fields of toxicology. In this field, ion beam techniques such as particle-induced X-ray emission has been mostly used in the evaluation of toxic element pollution in various regions of the world [88]. For example, one study used particle-induced X-ray emission to assess the levels of toxic elements in the vicinity of a mining area in Mongolia, which included places of milling, grasslands, and villages [89]. Among the samples tested, human hair was also used. The average concentrations of titanium, arsenic, and strontium were found to be higher in hair samples from miners than that of control participants. Besides studies related to environmental pollution, ion beam analysis has also been applied in toxicology research. For example in toxicology studies, mercury has completely overpopulated the literature [14].
\nElemental analysis of hair samples has also branched into the field of veterinary sciences. Interestingly, ion beam techniques have also been exploited in animal hair analysis. For example, particle-induced X-ray emission was employed to assess the levels of elements in the main hair of horses in a study aimed at investigating the relationship between main hair elemental concentrations and the severity of second degree atrioventricular block in horses [90]. The results showed that there was a significant positive correlation between the zinc/copper ratio and calcium concentration in main hair and the drop in ventricular beats measured hourly in animals with a second-degree atrioventricular block. Receiver operating characteristic curve analysis suggested that the cut-off points for hair calcium concentration were set at 1536 μg/g and 26.0 for the zinc/copper ratio in detecting second-degree atrioventricular block in horses. It was concluded that the levels of calcium, zinc, and copper in the main hair of horses may be used as a diagnostic tool for testing susceptibility to atrioventricular block.
\nToday, more and more studies connect metabolic homeostasis and morbidity with the complicated interaction between essential and nonessential elements [91]. However, disease may also perturb elemental levels and alter the expression of other chemical compounds in the body [14]. A good example here includes the effect of arsenic exposure on the reduction of glucose tolerance [92]. Elemental dyshomeostasis in the body will also affect hair metabolic processes and hence elemental levels within the actively growing hair.
\nA fundamental understanding of what for example elemental concentrations in hair actually describe still requires more rigorous research and debate. More specifically, more studies investigating the incorporation of chemicals into hair, for example how elemental levels relate to blood levels and other biomarkers of disease, and most importantly, the contribution of contaminants to biogenic hair elemental content, are required. When performing hair analysis, careful consideration of the various confounding factors in hair elemental analysis such as medication use, smoking, and seasonal diet fluctuations is also warranted [14, 93]. In essence, these considerations are imperative before the intricate link can be cemented between hair elemental concentrations and its biological significance related to morbidity or other factors.
\nStudies utilizing ion beam and synchrotron radiation techniques have, however, improved our understanding of the distribution of elements in hair tissue and elemental dyshomeostasis in disease [50, 80, 82]. Hair elemental analysis finds perhaps the most important application in toxicology research relating to acute versus chronic exposure to toxic metals and other xenobiotic compounds [80]. A fascinating example includes the case of the famous race horse Phar Lap in which synchrotron radiation XRF was used to confirm the cause of death [94]. Arsenic mapping in hair using synchrotron XRF and XAS not only allowed longitudinal distribution mapping of arsenic in the hair of Phar Lap, but also the retrospective changes in the metabolic incorporation of arsenic into the hair shaft. Another example includes the use of ion beam or synchrotron radiation analysis in epidemiological and etiological studies assessing exposure to toxic metals in vulnerable populations [14]. A recent exploratory study also pointed to the use of MeV-SIMS for the detection and mapping of the micronutrient lithium and its isotopes in longitudinally sectioned hair [53]. Lithium is an important psychopharmaceutical in the psychiatric community, and since it is quite challenging detecting the low Z element lithium that is present at trace levels in biological tissues, such analysis may find important application in monitoring medication adherence among psychiatric patients using hair. In summary, hair analysis remains a cost-effective baseline tool for not only more comprehensive studies linking morbidity with the chemicals and more specifically elements found in hair and vice versa, but also various other important applications in diverse fields. With the continuous development and optimization of ion beam and synchrotron radiation techniques, the future of hair analysis remains bright.
\nReducing the elements of integrated circuits (ICs) leads to an increase in the speed of the processors and an increase in the amount of memory, but at the same time the bandwidth between them varies only slightly. This is referred as the von Neumann bottleneck and often limits the performance of the system [1]. One possible solution to this problem is the transition of computing systems to an architecture close to the structure of a biological brain, which is a set of elements of low power connected in parallel neurons interconnected via special channels synapses [1, 2, 3, 4]. Processors built on this architecture have concurrent computing and will be able to surpass modern computers in tasks related to unstructured data classification, pattern recognition, as well as in applications with adaptable and self-learning control systems. One of the possible ways of implementing such an architecture is to manufacture ICs based on neuromorphic structures, which are memory elements in the form of cells (neurons) interconnected by data buses (synapses) and are capable of changing their electrical resistance under the influence of an external electric field (the effect of resistive switch) [1, 2, 3, 4, 5]. Such structures can maintain cell resistance after the termination of the external electric field and are the basis of non-volatile resistive memory (ReRAM). The advantages of ReRAM include small size, high degree of integration, low power consumption, and high speed, which allows on its basis to realize the mass parallelism and low power calculations observed in the study of biological brain [6, 7, 8].
Currently, active theoretical and experimental studies of the effect of resistive switching in nanomaterials and nanostructures are underway to create elements of the ReRAM self-learning adaptive neuromorphic processor with high speed and low power consumption. An analysis of the publications showed that for the manufacture of ReRAM, films based on binary metal oxides (SiOx, TiO2, ZnO, HfOx, etc.) are promising from which amorphous titanium oxide and nanocrystalline zinc oxide can be distinguished, allowing for high response speed of the resistive switching process [8, 9, 10].
The creation of ReRAM elements for a neuromorphic processor is associated with the development and research of the formation processes of structures with a nanometer resolution. Existing lithographic methods of semiconductor technologies are approaching the limit of their resolution, characterized by a high degree of complexity and cost of equipment. Therefore, there is a need for research and development of new methods, the use of which will allow the creation of nanostructures of ReRAM elements, including at the prototyping stage.
One possible way of ReRAM elements prototyping is probe nanotechnologies usage, which is a combination of methods for nanostructures forming using a probe tip with visualization and process control in situ. Promising methods of probe nanotechnologies for ReRAM elements prototyping include local anodic oxidation (LAO) and scanning probe nanolithography (SPN) of atomic force microscope.
The method of local anodic oxidation is promising for the manufacture of oxide nanostructures (ONS) of titanium, which have reproducible memristor effect and do not require forming [11, 12, 13, 14]. The advantages of the LAO method also include precision, the possibility of conducting research on electrochemical processes in local areas up to the size of several nanometers in situ diagnostics of the results of the formation of ONS on the substrate surface, the absence of additional technological operations for applying, exposing, and removing photoresist, as well as the relatively low cost of process equipment [15, 16, 17, 18, 19, 20]. A variety of nanoimprint lithography is scratching probe nanolithography, which allows using the tip of an atomic force microscope probe to form profiled nanostructures in polymer films [21]. The simplicity of the method implementation allows using it in the development and study of promising design and technological solutions for prototyping ReRAM elements [22].
At the present stage of nanotechnology development, one of the most promising methods for surface diagnostics is scanning probe microscopy (SPM). The use of SPM methods allows the study of the local geometric, electrical, and mechanical properties of the sample surface [23, 24, 25, 26].
Of interest for creating ReRAM with high cell density are memristor structures based on vertically aligned carbon nanotubes (VA CNTs) [27, 28]. The vertical orientation of the nanotubes provides a significant reduction in the memory cell area and the technology of producing VA CNTs based on the method of plasma-enhanced chemical vapor deposition (PECVD) allows localized growth of nanotubes in a process compatible with silicon technology [29, 30]. In addition, the use of VA CNTs as a storage element is expected to reduce the switching time to picoseconds [28, 31].
A promising method of probe nanotechnologies for creation and characterization of memristor structures based on VA CNTs is the scanning tunneling microscopy (STM) [26]. This method allows you to create a controlled elastic deformation in VA CNT, the presence of which is a prerequisite for the occurrence of the memristor effect in VA CNT [32]. The mechanism of memristive switching of strained carbon nanotube is described in detail in [28].
This chapter describes application of scanning probe microscopy techniques for determination of resistive switching effects in vertically aligned carbon nanotubes, TiO2 nanostructures, and ZnO thin nanocrystalline films. Described techniques can be used for formation and nanodiagnostics of parameters of memristor structures for creation of metal oxide and CNT-based neuromorphic system.
The memristor effect study was carried out on titanium oxide nanostructures (ONS) using AFM spectroscopy using SPM Solver P47 Pro. For this purpose, local anodic oxidation (LAO) was carried out on the thin titanium film surface with a 20 nm thickness, and as a result, titanium ONS was formed with lateral dimensions 1 × 1 μm and 1.1 nm thick (Figure 1).
Titanium oxide nanostructures, formed by LAO: (a) AFM image; (b) profilogram along the line; and (c) current-voltage characteristics measuring scheme.
Then, using the AFM, the current-voltage (I-V) characteristics of the obtained structure were measured according to the scheme shown in Figure 1c with the application of a triangular-shaped voltage pulse (Figure 2a inset). It was shown that the titanium ONS obtained by the LAO exhibits a bipolar resistive switching effect (Figure 2) without additional doping and electroforming operations.
Current-voltage characteristic of titanium ONS, formed by the LAO.
The analysis showed that the current-voltage characteristic type corresponds to the switching mechanism due to potential barrier width modulation at the electrode/oxide interface described in [11, 12]. In this case, the potential barrier modulation occurs alternately at both the electrodes boundaries.
Initially, the structure is in high resistance state (HRS) (1.3 GΩ at 3.5 V) in the forward bias region (region I in Figure 2), while at a negative voltage applied to −5 V, the structure is in low resistance state (LRS) (0.27 GΩ at −3 V) (region II in Figure 2). Then, as the voltage rises in the reverse bias region from −6 to −10 V, the structure is switched, resulting in a HRS state (3.4 GΩ at −3 V) at the reverse bias (region III in Figure 2) and LRS (0.35 GΩ at 3.5 V) at up to 5 V direct bias (region IV in Figure 2). With an increase in the applied voltage from 6 to 10 V, the structure is switched to the initial state. In this case, the structure resistance ratio in the HRS state to the LRS state for positive voltages is 3.6, and for negative voltages is 12.6.
For the experimental study, titanium ONS with 2 × 2 μm lateral dimensions and 6.8 nm thick was formed by LAO. Then, on its surface in the AFM contact mode was performed a spectroscopic measurement of dependence of the feedback circuit current on the cantilever beam bending. The spectrogram showed that with an increase in the feedback circuit current by 1.02 nA, the beam is bent by 20.8 nm. Since the cantilever beam stiffness is 2.5 N/m, it is possible to calculate the AFM probe pressing force to the ONS surface for a given feedback circuit current Figure 3.
Dependence of feedback circuit current from the cantilever beam bending.
Then, current-voltage characteristics were measured on the ONS surface in the ±10 V range with the AFM feedback circuit current values from 0.01 to 2 nA (Figure 4), after which the structure resistance values in the HRS and LRS states were measured at 3.5 V.
Dependence of titanium ONS resistance in the HRS and LRS states on the pressing force.
Obtained dependences analysis showed that an increase in the AFM probe clamping force to the surface from 0.51 to 102.8 nN leads to a decrease in the structure resistance in the HRS state from 1.12 × 1011 to 9.63 × 109 Ω and in the LRS state from 2.28 × 1010 to 1.38 × 109 Ω.
This dependence can be explained by the fact that with a clamping force increase, an increase in the contact area between the AFM probe and the oxide surface occurs. In further studies, 60 nN clamping force was used, ensuring reliable contact of the probe with the structure.
Literature analysis showed that the top electrode material has a significant impact on the resistive switching of memristor structures. To study this effect, the current-voltage characteristics were measured in the mode of current AFM spectroscopy on the surface of oxide nanostructures formed by the LAO method; AFM probes with different conducting coating were used as the upper electrode. The resulting characteristics are presented on (Figure 5).
Titanium ONS current-voltage characteristics, obtained using a cantilever coated by: (a) Pt; (b) TiN; and (c) carbon.
Obtained dependences analysis showed that the use of cantilevers with different coatings significantly affects the manifested memristor effect. So, when using a cantilever with a Pt coating, a symmetrical I-V characteristic was obtained (Figure 5a) with low current values, the structure resistance in the HRS state is 327 × 109 Ω, and in the LRS state is 22 × 109 Ω, while the resistance ratio in the high resistance to low resistance is 15.
When using a cantilever with a TiN coating, an asymmetric I-V characteristic was obtained (Figure 5b), while in the negative voltage region the memristor effect is insignificant, the structure’s resistance in the HRS state is 4.65 × 109 Ω, and in the LRS state −0.39 × 109 Ω, at the same time, resistance ratio in the high resistance to low resistance is 12. In the case of using a carbon-coated cantilever, an asymmetric I-V characteristic is also observed (Figure 5c), and there is no current through the ONS when applying voltages less than ±5 V in the case of a structure being in HRS and applying a voltage less than ±2 V in case of a structure being in LRS. The structure’s resistance in the HRS state is 1.74 × 109 Ω, and in the LRS state, it is 0.3 × 109 Ω, and the resistance ratio in the high resistance to low resistance is 6.
Study results showed that the platinum-coated cantilever use as the top electrode is characterized by a largest resistance ratio in the HRS and LRS states.
Another goal is to study titanium ONS thickness effect and applied voltage pulses on the memristor effect. For this, four ONSs were formed with lateral 2 × 2 μm dimensions and 1.6–3.6 nm height, which, based on the expression describing the oxide height and depth ratio presented in [3], corresponds to 3.6–8.2 nm thickness. The current-voltage characteristics were measured on these structures surface by applying ±2.4 voltage pulse (Figure 6).
Titanium ONS current-voltage characteristics with a thickness: (a) 3.6 nm; (b) 5.4 nm; (c) 7.2 nm; and (d) 8.2 nm.
Obtained expression analysis showed that with an increase in the ONS thickness, a decrease in the current corresponding to the LRS state and an increase in the resistance in this state are observed, to the extent that the memristor effect does not manifest itself when the oxide thickness is 8.2 nm.
The results allowed us to obtain voltage of the switching structure in the HRS state (Ures) and in the LRS state (Uset) dependence, as well as the corresponding currents (Ires and Iset) on the titanium ONS thickness (Figure 7). In addition, the dependence of the structure resistance measured in a HRS and LRS state on the ONS thickness measured at 1.5 V was obtained (Figure 8).
Dependence of electrical parameters of titanium ONS on the oxide thickness: (a) voltage and (b) current.
Dependence of titanium ONS resistance on the thickness.
It is shown that increasing the thickness from 3.6 to 8.2 nm increases the resistance in the HRS state from 1.4 × 1011 to 8.8 × 1011 Ω, while the resistance in the LRS state increases from 1.765 × 109 to 2.4 × 1011 Ω, while the structure resistance ratio in the high resistance to low resistance decreases from 79.4 to 3.6.
To study the applied voltage pulses amplitude effect on the memristor effect, an titanium ONS with 2 × 2 μm lateral dimensions and 3.6 nm thickness was formed. Then, its current-voltage characteristic was measured in the voltage range from ±1 to ±4 V (Figure 9).
Current-voltage characteristics of titanium ONS in the different voltage range: (a) ±1 V; (b) ±2 V; (c) ±3 V; and (d) ±4 V.
The analysis showed that when measuring the titanium ONS current-voltage characteristics with 3.6 nm thickness in the voltage range ± 1 V, the memristor effect is not observed, the structure shows the conductivity absence. When measuring the I-V characteristic in the ±2 V range, the structure also shows the conductivity absence, however, a small current surge in the I-V characteristic is already observed. When measuring the I-V characteristic in ±3 and ± 4 V range, this structure exhibits a memristor effect. It is shown that in the case of measuring the I-V characteristic in ±3 V range, the structure resistance in the HRS state is 39.2 × 109 Ω, and in the LRS state −1.4 × 109 Ω, the resistance ratio in the HRS and LRS states is 27.4. In the case of measuring the I-V characteristic in ±4 V range, the structure resistance the in the HRS state is 1.08 × 109 Ω, and in the LRS state it is 0.14 × 109 Ω, the resistance ratio in the HRS and LRS states is 7.5.
Such a memristor effect dependence on the titanium ONS thickness and the applied voltage pulses amplitude is explained by the electric field intensity influence in the oxide on the oxygen vacancies transfer in the oxide volume between the electrodes and the titanium ONS switching between high-resistance and low-resistance states.
A resistive switching effect in thin oxide films is attractive for manufacturing of neuromorphic system, which offers significant advantages over classical computers, such as an effective processing of data recognition. ZnO is the one of the promising materials, which is widely used in electronic element developments, sensors, and microsystem technology. Also, ZnO demonstrates resistive switching, which has just one phase and is compatible with semiconductor technology. To fabricate ZnO-based neuromorphic system, it is necessary to study resistive switching in ZnO films and today there are insufficient experimental results about it.
To investigate resistive switching Al2O3/ZnO:In (42.1 ± 5.6 nm) as a wafer was used. ZnO thin films were grown using pulsed laser deposition under the following conditions: wafer temperature: 400°C, target-wafer distance: 50 mm, O2 pressure: 1 mTorr, pulse energy: 300 ml. To provide electrical contact to the bottom ZnO:In electrode, ZnO films were deposited through a mask.
Electrical properties of obtained ZnO films were measured by Ecopia HMS-3000 equipment (Ecopia Co., Republic of Korea). Obtained ZnO films had electron concentration 8.4 × 1019 cm−3, electron mobility 12 cm2/V∙s, and resistivity 5.2 × 10−3 Ω∙cm.
AFM-images of the ZnO film surface were obtained in semi-contact mode using scanning probe microscope Solver 47 Pro (NT-MDT, Russia). The AFM-image processing was performed using Image Analysis software. Figure 10 shows experimental investigations of ZnO film morphology. It is shown that ZnO film surface has a granular structure (Figure 10a and c) with 1.53 ± 0.27 nm roughness (Figure 10b). The ZnO film thickness was measured by ZnO/ZnO:In stair scanning, and was equaled 32.3 ± 7.2 nm.
ZnO film surface: (a) AFM-image; (b) AFM cross-sectional profile on (a); and (c) phase.
Electrical measurements were taken using nanolaboratory Ntegra with W2C probes. During the resistive switching investigation, ZnO:In film was grounded.
Current-voltage curves (CVC) were obtained from −3 to +3 V sweep for 15 cycles at the same point and for 15 cycles at different points on ZnO surface (Figure 11a). Based on the results obtained, resistance dependence on cycle number (uniformity test) and resistance dependence on number point were built (homogeneity test). It was shown RHRS and RLRS were equaled to 0.68 ± 0.07 GΩ and 0.11 ± 0.04 GΩ, respectively at the same point on ZnO surface. At different points, RHRS and RLRS were equaled to 0.75 ± 0.13 GΩ and 0.12 ± 0.06 GΩ. RHRS/RLRS was equaled to 9.05 ± 5.65 at 0.7 V. Resistance dispersion during uniformity test was more than resistance dispersion during homogeneity test that can be explained by a granular structure of ZnO film.
Investigation of resistive switching in ZnO film: (a) current-voltage characteristic; (b) uniformity; and (c) variability.
Time stability of resistive switching in ZnO was implemented using Ntegra in two stages. On the first stage, charge structure was formed on the ZnO surface at +5 V (Figure 12a). On the second stage, charged structure was scanned in Kelvin mode in the interval from 5 to 30 minutes with a step 5 minute (Figure 12b and c). It was shown that voltage decreased from 266 ± 17 to 68 ± 7 mV in 30 minutes (Figure 12a).
Investigation of ZnO film surface charge: (a) Kelvin mode image of charged structure; (b) AFM cross-sectional profile on (a); and (c) time dependence of voltage.
Resistive switching element manufacturing is associated with the development and research of the formation processes of structures with a nanometer resolution. Existing lithographic methods of semiconductor technologies are approaching the limit of their resolution, characterized by a high degree of complexity and cost of equipment. Therefore, there is a need for research and development of new methods, the use of which will allow the creation of nanostructures of resistive switching elements, including at the prototyping stage. A promising method for the formation of nanoscale structures that can be used to create resistive switching elements is nanoimprint lithography based on the use of special dies and films of polymeric materials. A type of nanoimprint lithography is scratching probe nanolithography (SPN), which allows using the tip of an atomic force microscope probe to form profiled nano-sized structures in polymer films. It was decided to use photoresist FP-383 as polymer film, because it is cheaper and has longer shelf life compared to other types of polymer films.
The solution of photoresist/thinner (FP-383/RPF383F) at volume ratio of 1:10 was transferred onto Si substrate using the centrifugal method at the rotation speed of a Laurell WS-400B-6NPP centrifuge at 5000 rpm. After the deposition of the film, the photoresist/thinner film was dried at a temperature of 90°С for 25 minutes. Thickness of the photoresist/thinner film was equaled to 32.1 ± 4.7 nm.
Scratching probe nanolithography on the photoresist/thinner film was performed using a Solver P47 Pro scanning probe microscope. Indentation was performed by applying an AFM probe to the surface of a FP-383 film with a fixed clamping force (the Set Point parameter in the AFM control program). Thus, arrays of the seven profiled lines-grooves were formed at different nanoindentation forces (Figure 13).
Profiled nanostructures on photoresist surface: (a)AFM-image; and (b) AFM cross-sectional profile on (a).
Analysis of the results obtained showed that nanoindentation force increase from 0.5 to 3.5 μN leads to nanostructure-groove depth increase from 2.7 ± 0.8 to 25.31 ± 2.11 nm (Figure 14a), tip velocity increase from 0.1 to 5 μm/s leads to nanostructure-groove depth decrease from 25.10 ± 1.2 to 8.87 ± 1.34 nm (Figure 14b).
Investigation of scratching probe nanolithography regimes: (a) force of depth dependence; (b) velocity of depth dependence.
The nonlinearity of the dependences obtained can be explained by the inhomogeneity of the viscoelastic properties of the FP-383 film. It should also be noted that the nature of the contact interaction between the probe and the film is complex and is largely determined by the elastic forces.
To fabricate memristor structure, photoresist FP-383 thin film with thickness 21.4 ± 3.1 nm was formed on Al2O3/ZnO:In/ZnO substrate. Then squared nanostructure-groove was formed on FP-383 film surface using scratching probe nanolithography at nanoindentation force 3.18 μN (Figure 15). Thin Ti film was deposited using BOC Edwards Auto 500 system. After that lift-off process was applied using dimethylformamide. AFM-image of the Al2O3/ZnO:In/ZnO/Ti resistive switching structure obtained is shown in Figure 16. Analysis of the result obtained showed that Ti film thickness was equaled to 4.1 ± 0.3 nm (Figure 16b). Ripped edges of Ti structures are result of lift-off process.
Profiled nanostructure on FP-383 film surface: (a) AFM-image; and (b) AFM cross-sectional profile on (a).
Resistive switching Al2O3/ZnO:In/ZnO/Ti/W2C memristor structure: (a) AFM-image; (b) AFM cross-sectional profile on (a); and (c) phase.
Figure 17 shows current-voltage characteristic of Al2O3/ZnO:In/ZnO/Ti/W2C structure at −4 to +4 voltage sweep. It was shown that Al2O3/ZnO:In/ZnO/Ti/W2C structure has nonlinear, bipolar behavior when the electric potential gradient is the dominant parameter of resistive switching.
Investigation of resistive switching in Al2O3/ZnO:In/ZnO/Ti/W2C structure: (a) current-voltage characteristic; (b) uniformity; and (c) homogeneity.
Investigation of resistive switching of Al2O3/ZnO:In/ZnO/Ti/W2C structure in the single point (uniformity test) shown that RHRS was 8.23 ± 1.93 GΩ and RLRS was 0.11 ± 0.06 GΩ (Figure 17b). At different points, RHRS and RLRS were equaled 7.65 ± 2.83 GΩ and 0.18 ± 0.11 GΩ, respectively (Figure 17c). It was shown, that RHRS/RLRS coefficient was equaled 135.31 ± 44.38 at 0.7 V.
In the end, it was shown that the use of Ti film allowed to increase RHRS/RLRS coefficient from 9.05 ± 5.65 to 135.31 ± 44.38 and to decrease the resistance dispersion of resistance switching (Figures 11 and 17). It can be explained by exception for the influence of air oxygen in Al2O3/ZnO:In/ZnO/Ti structure that significantly worsens the resistive switching.
The dependence of the resistive switching of a vertically aligned carbon nanotube on the voltage pulse amplitude was studied using the STM spectroscopy using the probe nanolaboratory Ntegra. Figure 18 shows the current-voltage characteristics of a strained carbon nanotube, obtained by applying a series of voltage sawtooth pulses with amplitude of 1–8 V, duration of 1 second, and tunnel gap of 1 nm. The diameter of a VA CNT of the investigated array was 95 ± 5 nm, length 2.3 ± 0.2 μm, and density of nanotubes in the array was 18 μm−2. It should be noted that the current-voltage characteristics are represented in the range from 0 to 50 nA, which relates to the peculiarities of the measuring system of the scanning tunneling microscope.
CVCs of VA CNT upon application of a series of sawtooth voltage pulses with amplitude: (a) 2 V; (b) 4 V; (c) 6 V; and (d) 8 V.
The measurement results showed that resistive switching of the VA CNT does not occur when the applied voltage amplitude is less than2 V (Figure 18a). This is due to the insufficient value of the external electric field for the formation of a low-resistance state in the nanotube [28]. The reproducible resistive switching was observed with a further increase in amplitude to 4 V and more (Figure 18b–d). The RHRS/RLRS ratio increased from 1 to 52 with an increase in the amplitude U from 1 to 8 V. This dependence is explained by the fact that the nanotube had the same resistance values of RHRS, while the resistance of its low resistance state decreased inversely to the increase in the applied voltage amplitude due to the compensation of the internal electric field arising during deformation of the VA CNT with an external electric field [28].
It should be noted that the values of RHRS and RLRS of the VA CNT are 2–3 times lower at U < 0 than at U > 0. It is due to the fact that associated with the occurrence of a piezoelectric charge, internal field of the nanotube [33, 34] is co-directed with an external electric field, and accordingly, reduces the resistance of the VA CNT when a negative voltage is applied and is oppositely directed and increases the total resistance of the VA CNT when a positive voltage is applied.
The studies of the influence of deformation on resistive switching of a VA CNT were performed by the STM spectroscopy with a tunneling gap
CVCs of VA CNT at various values of deformation ΔL ≈ d and at voltage sawtooth pulses amplitude: (a) 4 V; and (b) 8 V.
Analysis of the obtained CVCs showed that at U = 4 V, the RLRS value initially decreased and increased again at ΔL = d = 2 nm (Figure 19a). This is due to the fact that the magnitude of the external electric field was not enough to compensate the internal electric field of the nanotube at a deformation of 2 nm. This effect disappeared as the voltage amplitude increased to U = 8 V due to an increase in the external electric field (Figure 19b). The values of RHRS and RLRS of the VA CNT decreased with increasing deformation (Figure 19b). The decrease in the of RHRS and RLRS of the VA CNT is due to the increase in the initial deformation ΔL ≈ d and the corresponding value of the piezoelectric charge, and is consistent with the mechanism of memristive switching of VA CNT [28].
It was also shown that the RHRS/RLRS ratio of the VA CNT does not depend on the deformation value and is determined by the value of the applied voltage: the RHRS/RLRS = 2–3 at U = 4 V (Figure 19a) and the RHRS/RLRS > 50 at U = 8 V (Figure 19b).
Thus, application of scanning probe microscopy techniques for fabrication and determination of electrical parameters of memristor structures based on vertically aligned carbon nanotubes, titanium oxide nanostructures, and nanocrystalline ZnO thin films was presented. It is shown that titanium oxide nanostructures obtained by local anodic oxidation have a memristor effect without additional electroforming. The regularities of the manifestation of the memristor properties of oxide nanoscale structures of titanium are established, and the effect of the thickness of oxide nanoscale structures and the amplitude of applied voltage pulses on the displayed memristor effect in them is shown. It was found that the oxide nanoscale structures of titanium with a thickness of 1.6 nm have a resistance ratio in the high resistance to low resistance equal to 79.4. By using scratching probe nanolithography was made memristor structure based on nanocrystalline ZnO thin film obtained by pulsed laser deposition. The results can be used for micro- and nano-electronic elements manufacturing, as well as memristor structures, ReRAM elements using probe nanotechnologies, and for metal oxide and VA CNT-based neuromorphic system fabrication. The results of the study of resistive switching of vertical aligned carbon nanotubes using scanning tunneling microscopy are presented.
The results were obtained using the equipment of Research and Education Center and the Center for collective use “Nanotechnologies” of Southern Federal University.
This work was financially supported by Russian Foundation for Basic Research (projects No. 16-29-14023 ofi_m, 18-37-00299 mol_a) and internal grant of the Southern Federal University (project No. VnGr-07/2017-26).
The authors declare no conflict of interest.
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The accumulated knowledge has shown turbulent flow to be composed of islands of vortices and uniform-momentum regions, which are coherent in both time and space. Research has been concentrated on these structures, their generation, evolution, and interaction with the mean flow. Different theories and conceptual models were proposed with the aim of controlling the boundary layer flow and improving numerical simulations. Here, we review the different classes of turbulence coherent structures and the presumable generation mechanisms for each. The conceptual models describing the generation of turbulence coherent structures are generally classified under two categories, namely, the bottom-up mechanisms and the top-down mechanisms. The first assumes turbulence to be generated near the surface by some sort of instabilities, whereas the second assigns an active role to the large outer layer structures, perhaps the turbulent bulges. 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The accumulated knowledge has shown turbulent flow to be composed of islands of vortices and uniform-momentum regions, which are coherent in both time and space. Research has been concentrated on these structures, their generation, evolution, and interaction with the mean flow. Different theories and conceptual models were proposed with the aim of controlling the boundary layer flow and improving numerical simulations. Here, we review the different classes of turbulence coherent structures and the presumable generation mechanisms for each. The conceptual models describing the generation of turbulence coherent structures are generally classified under two categories, namely, the bottom-up mechanisms and the top-down mechanisms. The first assumes turbulence to be generated near the surface by some sort of instabilities, whereas the second assigns an active role to the large outer layer structures, perhaps the turbulent bulges. Both categories of models coexist in the flow with the first dominating turbulence generation at low Reynolds number and the second at high Reynolds number, such as the case in the atmospheric boundary layer.",book:{id:"7214",slug:"turbulence-and-related-phenomena",title:"Turbulence and Related Phenomena",fullTitle:"Turbulence and Related Phenomena"},signatures:"Zambri Harun and Eslam Reda Lotfy",authors:[{id:"243152",title:"Dr.",name:"Zambri",middleName:null,surname:"Harun",slug:"zambri-harun",fullName:"Zambri Harun"},{id:"252195",title:"Dr.",name:"Eslam",middleName:null,surname:"Reda",slug:"eslam-reda",fullName:"Eslam Reda"}]},{id:"63811",title:"Performance Analysis of FSO Systems over Atmospheric Turbulence Channel for Indian Weather Conditions",slug:"performance-analysis-of-fso-systems-over-atmospheric-turbulence-channel-for-indian-weather-condition",totalDownloads:1204,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Free-space optical (FSO) communication is a line of sight (LOS) technology and has significant advantages and attractive applications. Recently, spectrum slicing wavelength division multiplexing (SS-WDM)-based FSO systems provide improved link range, high capacity, and efficiency. In this chapter, the SS-WDM-based FSO system is proposed with four channels to increase the performance of communication under various wind speed and heights of the buildings. But, atmospheric turbulence fading, scintillation, and pointing errors (PE) are the main impairments affecting the performance of FSO communication systems. Predominantly, the turbulence variation due to wind velocity, refractive index, and height of buildings has been majorly focused and analyzed for Vellore weather conditions. A case study has been experimented on how the height of buildings and the atmosphere around VIT, Vellore campus, affect the transmission of light in free space. The bit error rate of the proposed system is analyzed with distance, received power for various wind speed and different heights of the buildings.",book:{id:"7214",slug:"turbulence-and-related-phenomena",title:"Turbulence and Related Phenomena",fullTitle:"Turbulence and Related Phenomena"},signatures:"Prabu Krishnan",authors:[{id:"243249",title:"Dr.",name:"Prabu",middleName:null,surname:"K",slug:"prabu-k",fullName:"Prabu K"}]},{id:"61221",title:"Laser Beam Propagation through Oceanic Turbulence",slug:"laser-beam-propagation-through-oceanic-turbulence",totalDownloads:898,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Using a recently proposed model for the refractive index fluctuations in oceanic turbulence, optical beam propagation through seawater is explored. The model provides an accurate depiction of the ocean through the inclusion of both temperature and salinity fluctuations to the refractive index. Several important statistical characteristics are explored including spatial coherence radius, angle-of-arrival fluctuations, and beam wander. Theoretical values of these parameters are found based on weak fluctuation theory using the Rytov method. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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