\r\n\tThe objective of this book is to provide a state-of-the-art review of the use of timber in building construction from various perspectives, including manufacturing, fabrication, modeling, design, and construction of residential and other types of buildings. Of special interest will be contributions related to new developments in timber technologies, design, construction, testing, sustainability, LCA, building envelope, and the performance of timber buildings in natural and man-made hazard conditions.
",isbn:"978-1-83768-263-8",printIsbn:"978-1-83768-262-1",pdfIsbn:"978-1-83768-264-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"356565153fc7e43f1bf0cb7ba5e7b28a",bookSignature:"Prof. Ali M. Memari",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12057.jpg",keywords:"Wood, Lumber, Timber Industry, Home Building, Glue-Laminated Wood, Cross-Laminated Timber, Plywood, Fire Resistance, Sustainability, Fabrication, Panelized/Modular, Material Properties",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 31st 2022",dateEndSecondStepPublish:"June 28th 2022",dateEndThirdStepPublish:"August 27th 2022",dateEndFourthStepPublish:"November 15th 2022",dateEndFifthStepPublish:"January 14th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"8 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Memari is a Professor and Bernard and Henrietta Hankin Chair in Residential Building Construction in the Departments of Architectural Engineering and Civil and Environmental Engineering. During his 30 years of teaching in structural engineering, his research focused on the behavior of structural, architectural, and enclosure components of residential and commercial buildings under natural hazard loading and environmental conditions. He has published over 300 publications.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"252670",title:"Prof.",name:"Ali",middleName:null,surname:"M. Memari",slug:"ali-m.-memari",fullName:"Ali M. Memari",profilePictureURL:"https://mts.intechopen.com/storage/users/252670/images/system/252670.jpg",biography:"Dr. Memari is a Professor and Bernard and Henrietta Hankin Chair in Residential Building Construction in the Departments of Architectural Engineering and Civil and Environmental Engineering at Penn State, and Director of The Pennsylvania Housing Research Center. 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1. Introduction
A biosensor is a device that uses specific biochemical reactions mediated by isolated tissues, enzymes, immunosystems, organelles or whole cells to detect chemical compounds (IUPAC: http://goldbook.iupac.org/B00663.html). Biosensors integrate two functions, i) a bio-receptor functionalized with probes able to specifically recognize the targeted species and ii) a transducer converting the specific biological interaction into a quantitatively measurable signal. One way to classify biosensors relates on the transduction mode, such as optical (fluorescence, surface-enhanced Raman scattering, chemiluminescence, colorimetry, dual polarization interferometry and surface plasmon resonance), electrochemical (amperometry, potentiometry, field-effect transistor and conductimetry) and gravimetric transduction (quartz crystal microbalance, cantilever) (Sassolas et al., 2008).
The evaluation of biosensor performances relies on the following criteria: high sensitivity, operational and linear concentration range, detection and quantitative determination limits, high selectivity, steady-state and transient response times, sample throughput, reliability, reproducibility, stability and long lifetime (Thévenot et al., 1999). Other aspects like cost of test, ease of use, time of analysis including all the steps required for sample preparation should also be taken into account. Some biosensors are based on the use of labels such as colorimetric, fluorescent, enzymatic moieties or redox species... However, the current trends aim to develop on-chip integrated and label free detection systems. In this framework, porous silicon (PSi) offers high potential for biosensing:
PSi physical properties directly depend on the structure. The optical properties are linked to the variation of refractive index with a change of porosity while the electrochemical properties rely on surface chemistry modification. Thus, PSi based transducers can be sensitive both to surface or volume biomolecular recognition.
PSi surface chemistry is essentially governed by the high reactivity of Si-H bond, which can form both Si-alkyle or Si-OH bond (Stewart & Buriak, 2000). Thus, the surface can be either hydrophobic or hydrophilic, and a large range of biomolecules can be immobilized.
The porosity of PSi can vary from 15 to 90%, yielding high specific surface and pore size ranging from nanopores (< 2 nm) to macropores (> 50 nm) (Canham, 1990). Mesopores (with 2-50 nm diameter) are the most suitable for biosensing, because they are large enough to allow for good biomolecule diffusion and they yield large specific surfaces ranging from 100 m2/g to 350 m2/g, which strongly increases the amount of biomolecules that can be immobilized on the transducer compared to a 2D surface immobilization. It is worthwhile to point out that the accessibility of the probes by the target molecules (to be detected) depends both on the pore size and on the surface energy of PSi (Tinsley-Bown et al., 2000).
Finally, PSi is fully compatible with standard microprocessing techniques and can be micromachined, etched, and on-chip integrated.
The scope of this chapter is to present new concepts of integrated PSi biosensors, as well as the tools used for their study and realization, and a discussion on their performances.
2. Biosensors based on porous silicon
In the field of biosensors, PSi is mainly used for its large surface area. As an example, functionalized PSi was used in a modified single-tube format chemiluminescent assay to catalyze an enzymatic reaction indicating the presence of Escherichia coli bacteria. A lower detection limit of 10 cells within 40 min was obtained using PSi, compared to 103 cells for “classical” tube chemiluminescence assay (Mathew & Alocija, 2005). PSi thin films functionalized with covalently grafted antibodies were also used to selectively capture dye-labelled MS2 bacteriophage viruses (Rossi et al., 2007). Although pore penetration and binding efficiency depend on PSi surface wettability, fluorescence measurements showed a detection limit of 2x107 pfu/ml (pfu: plaque-forming units) and a dynamic range for the measurement of viral concentrations from 2x107 to 2x1010 pfu/ml. In these two cases, the targeted species are detected by chemiluminescent or fluorescent intensity measurements.
Biosensors can be advantageously based on electrical or electrochemical transducer properties when the biological recognition involves the conversion of an electroactive substance in contact with the target to be detected, e.g., in the case of enzymatic reaction. The current generated by electron transfer can be directly measured by amperometry if a conductive working electrode is used. A limiting factor for the sensitivity and the dynamic range is the amount of catalyzing species entrapped at the surface of the working electrode. Hence, a way to improve amperometric biosensor performances is the enlargement of the electrode area. Using a platinum-coated PSi layer to determine cholesterol concentration, a 3-fold increase of sensitivity was obtained compared to a planar electrode (Song et al. 2006).
A second class of electrical biosensors takes advantage of the semiconducting properties of Si substrates. In 1970, it was shown that a Field Effect Transistor (FET) can be adapted to work in aqueous media to build a so-called ISFET device that is sensitive to the ionic interactions with the SiO2 surface (Bergveld, 1970). In the ENFET proposed in 1980, the sensing surface of FET is modified with enzymatic species (Caras & Janata, 1980). In 1994, we proposed the GENFET, a device using the intrinsic properties of negatively charged DNA strands for in-situ and direct label-free detection of DNA hybridization (Martin et al., 1994). In order to detect simultaneously different DNA sequences, we showed that the photopotential of electrolyte/SiO2/Si semiconducting device is sensitive to the variation of the surface charge induced by DNA hybridization and could be used as a transducer for DNA chips (Souteyrand et al., 1997, 2000). In 1996, a PSi layer was added at the surface of the bulk Si potentiometric device to measure penicillin concentration. An enlarged linear range of the calibration curve and higher signals were obtained, which were attributed to the larger amount of enzyme immobilised on the PSi substrate compared to planar structures (Thust et al., 1996, 1999). To conclude, in the case of electrical transducers, the improvement of biosensor performances achieved with PSi layers is usually only due to an increase of the specific working area and not to improvement of the electrical properties.
In the case of label-free optical detection, biosensors exploit the refractive index variations induced by the presence of target biomolecules specifically bound to probes immobilized at the sensor surface. Among the large family of PSi optical biosensors, the simplest devices are Fabry-Perot interferometers constituted of a few μm-thick PSi monolayers. Large shifts of the interference fringes induced by the binding of target molecules have been observed for a large variety of molecules such as DNA, proteins or small organic biomolecules (Lin et al., 1997). Multilayer structures exhibiting high reflectivity in well-defined frequency ranges, such as Bragg mirrors (Rendina et al., 2007) or rugate filters (Chapron et al., 2007; Cunin et al., 2002), have also been widely studied for biosensing applications. These devices usually yield increased sensitivity due to multiple reflections of light within the multilayers, which enhance light-matter interactions. When a layer is introduced inside the multilayer structure with a different width or a different porosity from the PSi layers constituting the multilayer, a microcavity is built. Such a device enables to obtain very narrow resonances that are highly confined inside the microcavity and thus are very sensitive to any variation in refractive index induced by the presence of target biomolecules in this layer. It has been demonstrated that molecule layers as thin as 0.01 nm could be detected using microcavities (Ouyang et al., 2006). These devices are also suitable for antibodies detection in whole blood samples with high specificity and good sensitivity (Bonanno & DeLouise, 2007).
As an alternative to biosensors based on multilayers, planar waveguides have also been proposed. They consist of a thin waveguiding layer with medium porosity on top of a highly porous substrate. Contrary to interferometers or multilayers that are usually used at normal incidence, planar waveguides support light modes that are propagating within the waveguide parallel to the surface. These modes are confined by total internal reflection due to the refractive index difference between the waveguide and the surrounding air or the highly porous substrate, respectively. In order to excite such propagating modes, light is usually coupled through a prism at very particular incidence angles. Refractive index variation in the waveguide layer can be observed by monitoring the variation in coupling angle. Very high sensitivities corresponding to detection limits of 5 pg/mm2 have been reported using such sensors for DNA detection (Rong et al., 2008).
In the PSi-based optical biosensors cited above, red shifts are usually expected because the presence of the target biomolecules should increase the PSi refractive index. However, it has been demonstrated that a competing mechanism can lead to strong blue shifts. If Si-H or Si-OH bonds are present on the PSi surface, a transfer of negative charges from the bound molecules to the PSi can catalyze oxidation by the surrounding water molecules and results in strong corrosion of the PSi, thus in strong reduction of refractive index. The resulting blue shifts have often been observed in the case of DNA hybridization (Lin et al., 1997), and DNA biosensors based on catalytic corrosion were proposed and shown to yield much higher sensitivities than red-shift sensors (Steinem et al., 2004). The transduction mechanism was recently generalized to non-charged molecules by oxidation hydrolysis via metal catalysts in presence of oxidants, and avidin detection on biotinized PSi surfaces was demonstrated (Völcker et al., 2008). It is important to point out that this type of biosensors is restricted to single-use, as the corrosion leads to destruction of the PSi structure.
More complete reviews on PSi-based biosensors (Jane et al., 2009) or on label-free optical biosensors (Fan et al., 2008) can be found in the literature.
3. Novel photonic-crystal-based biosensors
As presented above, most PSi optical sensors share the particularity that their active region for sensing is either buried – e.g., micro-cavities in multilayers – or very thick – as in the case of interferometric devices. This leads to limitations of the diffusion of biomolecules inside the porous structure, which introduce delays in the device response and alter the optical properties due to in-depth inhomogeneity of infiltration. These issues can be reduced if the sensing layer is at the device surface and relatively thin, as in the case of planar waveguides.
The sensitivity of such planar sensors could be greatly enhanced if the surface configuration of planar waveguides could be combined with stronger light confinement and/or strong slowing down of light in order to increase light-matter interactions. The use of gratings (Ryckman et al., 2010) constitutes a first step towards improving the optical properties. Another way is to design new sensors using photonic crystals (PCs) concepts.
Photonic crystals are periodic arrangements of dielectric media (Joannopoulos et al., 1995; Viktorovitch et al., 2007, 2010). The periodicity can be either along one direction for one-dimensional (1D) PCs, in a plane for two-dimensional (2D) PCs, or in all dimensions for three-dimensional (3D) PCs. In this sense, periodic multilayers such as Bragg mirrors constitute 1D PCs. PCs have the great property to exhibit band structures for photons, i.e., light in such structures can only have discrete frequency states called photonic bands. Convenient engineering of photonic bands enables to control light velocity. Moreover, photonic band gaps (PBGs) can exist, i.e., frequency regions where light propagation is prohibited inside the PC. Hence, through a careful design of the PC it is possible to tailor its optical properties in order to strongly confine light in a given region of the device and to strongly reduce its propagation velocity.
In the following, we will present two different concepts of planar biosensors using PCs properties to increase sensitivity: a surface wave biosensor and a planar 1D PC device.
3.1. Surface-wave biosensor
The surface wave (SW) biosensor consists of a periodic multilayer with a defect layer at its surface. It can be understood as a hybrid between a planar waveguide and a microcavity device. Similarly to the planar waveguide, light can be excited within the PSi structure, e.g. through a prism, and confined due to the refractive index contrast between the dielectric structure and the lower-index environment. Similarly to the microcavity sensor, the periodic multilayer exhibits a PBG which prohibits light propagation inside the multilayer. Hence, light excited in such a device is forced to propagate within the thin defect top layer, leading to very strong light confinement and intensity within this surface layer. The sensitivity of SW devices has already been demonstrated for sensing applications (Liscidini & Sipe, 2007; Shinn & Robertson, 2005). It can be enhanced further if the devices are made in a material with much greater specific surface like PSi (Guillermain et al., 2006, 2007).
The principle of the SW biosensor is illustrated in fig. 1. Light is coupled to the PSi device through a prism. In this configuration, the SW can only be excited at a given frequency for a particular angle of incidence θ0, when its wave vector is matching the parallel wave vector of the incident beam inside the prism. At the particular angle of incidence θ0, most light is coupled to the SW, leading to a strong intensity decrease of the reflected beam. As the coupling conditions to the SW strongly depend on the surface layer configuration, in particular its refractive index, any change in refractive index induced by the presence of the target molecules should lead to a variation of the coupling angle, as illustrated in fig. 1b.
Figure 1.
Principle of the surface wave sensor: (a) device description, and (b) principle of optical sensing.
When compared to planar waveguides, the SW device presents the great advantage that the top layer can be of any porosity, provided that the layer thickness is correspondingly adjusted to optimize the optical properties. This means that the porosity of the top layer can be chosen depending on the size and properties of the biomolecules to detect. This is not the case in planar waveguides where the porosity of the top layer is limited, since the refractive index of the waveguide should be higher than that of the underlying PSi substrate. Moreover, we will demonstrate in section 6.1 that strong decrease of light velocity can be achieved via a lateral patterning of the multilayer with air slits as shown in fig. 1a, leading to strong enhancement of the biosensor sensitivity (Jamois et al., 2010a).
In the configuration shown in fig. 1a, the surface of the PSi device is facing the prism. In the case where in-situ experiments should be performed, the same biosensor could be used, provided that it is reported onto a transparent substrate in order to couple light from the backside and leave the PSi device in contact with the analyte.
3.2. Planar photonic-crystal biosensor
The planar 1D PC biosensor consists of a PSi layer with low or medium porosity on top of a higher-porosity substrate. As illustrated in fig. 2a, the top layer is patterned by a periodic array of air slits that extend in the depth down to the underlying porous substrate. When excited by a light beam at normal incidence, such a device can support particular modes, called Fano resonances that result from the coupling between the discrete bands of the 1D PC and the continuous states of the surrounding medium seen by the incident beam. These resonances are highly confined within the top layer and can have very high spectral finesse (Jamois et al., 2010b; Viktorovitch et al., 2007, 2010). If the device is conveniently designed, the excitation of the Fano resonance can lead to a complete switch of the reflectivity from zero reflection (i.e. complete transmission) to total reflection. Hence, any change in the refractive index of PSi induced by the presence of target molecules will lead to a shift of the resonance and to an abrupt change of reflectivity, as shown in fig. 2b.
Figure 2.
Principle of the planar photonic crystal sensor: (a) device description, and (b) principle of optical sensing.
This type of biosensor presents the advantage to be used at normal incidence with relatively simple optical setups and no need for a prism. It can be directly integrated into an optical microchip in case multiple parallel sensing is desired. As will be discussed later in this chapter, its fabrication is easier than for the surface wave device, since only the top layer is patterned in this case.
The biosensor configuration presented in fig. 2 aims at monitoring reflection properties. This is the configuration that will be considered in the following sections. However, the same device could also be used in transmission, provided that it is reported onto a transparent substrate. Transmission configuration is particularly interesting when in-situ measurements are desired, as it prevents the incident beam from going through the analyte, which could lead to strong light absorption and sensitivity decrease. In-situ measurements could also be performed in reflection configuration if the design of the biosensor is carefully optimized in order to position the resonance in a wavelength range where the analyte absorption is low.
4. Experimental realization
The experimental realization of the PC-based biosensors requires several main steps. The first step is anodization of the substrate to form the PSi layers. It is the focus of section 4.1. Anodization is followed by lateral patterning of the PSi using standard nanolithography and dry etching techniques in order to fabricate the PC, as will be detailed in section 4.2. After cleaning of the PSi devices to remove the remains from the patterning process, the PSi structure is slightly thermally oxidized (≤ 1 nm SiO2) in order to enable subsequent silane-based functionalization. The details of PSi functionalization are discussed in section 4.3. In the following, we will consider the case of DNA sensing via hybridization of single-strand DNA targets with their complementary strands immobilized on the PSi surface. After immobilization of the DNA probes, the last required step is a capping to prevent non-specific absorption. The main steps in the biosensor realization are summarized again below:
The influence of each step on the optical properties of the PSi is characterized by reflectivity measurements on 5 μm-thick PSi monolayers. After each step, the amounts of molecules infiltrated inside the pores can be quantitatively evaluated by fitting the reflectivity spectra with the refractive index models presented in section 5.1. The success of DNA immobilization and hybridization has also been verified by fluorescence measurements using probe and target molecules labelled with Cy3 and Cy5, respectively.
4.1. Porous silicon anodization
Anodization of silicon substrates to produce PSi is a well-described process in the literature. It takes place in hydrofluoric acid (HF) solution, where the silicon is dissolved by the fluorine ions thanks to the positive charges reaching the electrolyte/silicon interface (Kochergin & Föll, 2009; Lehmann & Gösele, 1991). Depending on substrate doping, current density and electrolyte concentration, the porosity and morphology of the fabricated PSi can be varied (Lehmann et al., 2000). In particular, PSi structures constituted of successive layers with different porosities, such as planar waveguides or multilayers, can be fabricated by controlled variation of the current density during anodization.
Fig. 3a shows a schematic view of the cell used to prepare our PSi samples. In order to fabricate meso-PSi, highly P-doped silicon substrates are used. The substrate is placed at the bottom of the anodization cell on a copper electrode, and in contact with the HF/H2O/ethanol (35%/35%/30%) electrolyte. The second electrode made of platinum is immersed in the electrolyte at the top of the cell.
When preparing PSi layers for optical application, good care has to be taken that the roughness at the interfaces between the layers is low enough to prevent light scattering. Hence, anodization takes place at low temperature (-40 C) in order to enhance the viscosity of the electrolyte, which has been shown to strongly reduce interface roughness (Setzu et al., 1998). Working at low temperature also allows for a better control of the anodization velocities, thus for a better control of the layer thicknesses. Fig. 3b presents a scanning electron microscope (SEM) picture of a fabricated SW device consisting of PSi layers with alternative porosities of 80% and 35% and a small surface layer with 35% porosity. In spite of the roughness due to sample cleaving, very smooth interfaces between the layers can be seen. The surface layer has a well-controlled thickness as thin as 60 nm.
After fabrication, the PSi structures are systematically characterized by reflectivity measurements in the 900-1700 nm infra-red range, in order to check the porosity, layer thickness and homogeneity. Fits of the reflectivity spectra are performed using the refractive index models and the optical simulation methods presented in section 5.
Figure 3.
a) Schematic view of the anodization cell used to prepare the PSi samples, and (b) SEM picture showing an example of PSi multilayer.
4.2. Porous silicon patterning
After fabrication of the PSi layers, the next step in biosensor realization is PSi patterning to build the PC devices. The challenge here consists in deeply patterning a material that is itself nanostructured, anisotropic, and highly insulating, at a submicron scale. The desired air slits should have perfectly vertical walls, a typical width of 200 to 400 nm, a period below 1 μm, and an aspect ratio – i.e. depth/width ratio – of 2 to 4.
Different ways have been explored to obtain patterns in PSi at a submicron scale. Among them, photo-dissolution appears to be a promising technique, which uses holographic setups to create light patterns into the material and locally dissolve the material (Lerondel et al., 1997). Similarly, photo-oxidation has also been proposed as an alternative to locally oxidize and selectively etch patterns into PSi layers (Park et al., 2008).
Different nanoimprint techniques have also been proposed, such as soft lithography where PSi is put in contact with a polymer stamp and selectively detached from the substrate (Sirbuly et al., 2003). Very recently, patterning of PSi layers via nanoimprint using silicon stamps has been proposed (Ryckman et al., 2010). This technique allows for the realization of very well defined gratings; however, the PSi inside the patterns might get damaged. The pattern aspect ratio that can be reached using imprinting techniques is also quite limited.
In order to reach the desired depth required for our PC devices, a patterning process based on electron-beam lithography and reactive ion etching (RIE) has been selected. Very few reports on PSi patterning using dry etching techniques can be found in literature. The processes proposed are based on fluorine (Arens-Fischer et al., 2000; Tserepi et al., 2003) or chlorine plasmas (Meade & Sailor, 2007) and have been used to realize patterns with widths in the 10-100 μm range. In spite of these encouraging achievements, PSi patterning at sub-micrometer scale with high aspect ratios remains a real challenge for many reasons: the porous nanostructure of the material and its anisotropic morphology leading to poor efficiency in the case of such directional etching processes, the large internal surface of PSi favouring high sensitivity to contaminations such as polymer deposition during plasma etching, as well as the strongly insulating nature of the material.
The different steps in the realization of the PSi PCs are presented in fig. 4. After fabrication of the PSi by anodization, a silica layer is deposited by sputtering. This layer serves a triple purpose, since it helps homogenising the surface of the sample for subsequent resist spin-coating and lithography, it prevents the resist from penetrating into the material pores, and it is used as a hard mask for RIE. After deposition of the silica layer, electron-beam lithography is carried out using PMMA A4 resist, and the resist patterns are transferred into the underlying silica layer by a CHF3-based RIE process. The patterned silica layer is then used as a hard mask for PSi etching which occurs in SF6/Ar plasma.
Figure 4.
The different steps of the patterning process used to realize PCs in PSi.
After careful optimization of each step of the PC realization process, in particular PSi patterning in SF6-based RIE, deep trenches with vertical walls and aspect ratio of about 2 were successfully etched into the PSi. Fig. 5a shows an example of trenches realized in a PSi structure constituted of two layers with different porosity, 35% and 80% for the top and bottom layer, respectively. It can be observed that the RIE process enables to etch both porosities with perfectly vertical walls and no visible transition between the two layers in spite of their very different morphological and electrical properties.
The etching efficiency of the RIE process strongly decreases with increasing porosity. Hence, the pattern depth that can be reached is limited in the presence of 80% porosity layers, and the process presented above has to be adapted to allow for the devices fabrication.
In the case of planar PC fabrication where only the top layer with 35% porosity is patterned, the limitation in etching efficiency is induced by the presence of the underlying highly-insulating 80%porosity substrate. In order to reach deeper patterns, anodization of the high-porosity substrate can be performed after patterning of the top layer. Fig. 5b shows a SEM view of a fabricated planar PC device which consists of a 700 nm-thick PSi layer with 35% porosity on top of a substrate with 80% porosity. The width and period of the trenches are 400 nm and 900 nm, respectively. The high-porosity substrate was anodized after patterning of the top layer. A very smooth interface between the two porous layers can be observed.
In the case of the SW device, much deeper trenches are required, since at least 3 multilayer periods should be patterned. A well-known way to achieve deep etching is to use cyclic processes including passivation steps to provide both sidewall verticality and protection of the etching mask. However, such a process should be avoided in the case of PSi, as it would lead to strong polymerization inside the PSi pores that would harden considerably the material etching over time, as well as prohibit any subsequent biochemical functionalization. In order to reach the desired number of patterned multilayer periods, a new process using a more selective hard mask has to be developed. One way would be to consider metallic masks; however, the issue of metal contamination of the internal PSi surface exposed to the RIE environment has to be carefully investigated, as it may also influence subsequent biochemical functionalization.
Figure 5.
a) SEM image showing a preliminary result of patterning of PSi layers with different porosities P1 (80%) and P2 (35%). (b) SEM images of fabricated planar PC in PSi. The period of the patterns is 900 nm, and the device has a total size of 100 μm x 100 μm.
Another issue to tackle is the contamination of the PSi by fluorine during the RIE process. Indeed, the fluorine contained in the plasma can react with inevitable carbon contamination to form a fluorocarbon layer that deposits onto the PSi walls in the depth of the material. Special treatments are currently under development to clean the PSi walls from this contamination. Anodizing the substrate after RIE like in the case of the planar PC device is also a good way to avoid this contamination.
4.3. Porous silicon functionalization for DNA sensing
The bioselective element of biosensors is usually based on the immobilization of biomolecules on the surface of the transducer. The immobilization reaction can be achieved by physisorption through weak interactions (van der Waals, coulombic forces), by crosslinking with glutaraldehyde via an aminated surface (Rong et al., 2008) or SMCC via a thiolated surface, by entrapment or by chemisorption via covalent bonding.
Covalent immobilization reactions of biomolecules require chemical functionalization of the surface. These chemical groups can be introduced by plasma, polymer coatings… Hetero-cross linkers are also widely used. These molecules have two functional groups: one reacting with the material and one reacting with the biomolecules to be immobilized.
PSi has already been used as a large surface area matrix for immobilization of different kinds of biomolecules including enzymes (Drott et al., 1997), DNA fragments (De Stefano et al., 2007) and antibodies (Betty, 2009). Chemical functionalization of PSi can either involve the native Si-H terminated surfaces or the Si-O bond resulting from PSi oxidation.
Native Si-H surfaces can lead to Si-C or Si-Si bonds via organometallic reactions or via dehydrogenative silane coupling, respectively (Stewart & Buriak, 2000). The hydrosilylation reaction of alkyne and alkene with Si-H leads to the formation of Si-C bond with reduction of the C-C multiple bond. It proceeds with appreciable rate in the presence of white light, Lewis acid or by thermal activation. Similarly, formation of Si-C can be obtained by reaction of Grignard (Stewart & Buriak, 2000) or by electrografting reactions with organo halide (Gurtner et al., 1999) or alkyne (Robins et al., 1999). Si-C bonds can also be formed by cleavage of Si-Si linkage by reacting organolithium (Kim & Laibinis, 1998) or by electrochemical reduction of alkynes (Robins et al., 1999).
Oxidation of silicon results in the incorporation of oxygen, leading to a surface bearing terminal silanol groups. These groups can readily react with silazane, alkoxy silane or organo silyl halide to form a siloxane bridge Si-O-Si. Organo silane can be mono or multifunctional (tri or di-chloro or -alkoxysilane). Multifunctional silane is usually preferred due to its higher reactivity and because it can lead to lower non-specific binding. Silanization with aminopropyl triethoxy silane or 3-glycidopropyl trimethoxy silane is well documented in the literature (Dugas et al., 2010a).
With multifunctional silane, additional intermolecular dehydration reactions between adjacent organo silanols lead to a 2D network. This polycondensation reaction needs to be perfectly monitored, otherwise it will lead to an anarchic 3D network and consequently to non-reproducible surface chemistry and obstruction of the PSi pores. An alternative solution is the use of monofunctional silane. Indeed, in this case each silane molecule can only react with the surface to form a siloxane bridge or with another silane molecule to form a dimer (Dugas et al., 2010b). The dimer is eliminated by subsequent washing. Therefore, no polymeric network is formed. The lower reactivity of monofunctional silane can be compensated by the use of silazane groups allowing for the complete reaction of all surface accessible silanols as demonstrated by Dugas (Dugas & Chevalier, 2003). The obtained layer was demonstrated to be reproducible and stable under harsh conditions.
Our process uses a monofunctional silane, tert-butyl-11-(dimethylamino)silylundecanoate which is an organo silazane bearing an ester function. Chemical functionalization of silica (Bras et al., 2004), PSi (Bessueille et al., 2005) and glass have been reported using this molecule from solution in pentane or from gas phase (Phaner-Goutorbe et al., 2011). As illustrated in fig. 6, after silanization, the tert-butyl ester is converted into the corresponding carboxylic acid by acidolysis in formic acid and activated with N-hydroxy succinimide. The obtained NHS ester surfaces can be employed for amine coupling. The resulting surface has a molecule density of 2x1014 molecules/cm². Immobilization of amino-modified oligo-nucleotide from diluted solution (25 µM) yielded to 3 – 4x1011 strands/cm². Hybridization yield with single stranded synthetic oligonucleotide is 10-20% (Dugas et al., 2004).
Figure 6.
Amino modified oligonucleotide are covalently immobilized by formation of an amide bond. After surface silanization with the monovalent silane uses tert-butyl-11-(dimethylamino)silylundecanoate (a), the tert-butyl ester group is removed leading to the corresponding carboxylic function (b). Activation (c) with diisoprpyl carbodiimide/ N-hydroxysuccinimide allows for the reaction with amino modified oliganucleotide (d) leading to the formation of an amide bond.
Modelling of PSi based PCs includes two different aspects: the calculation of the refractive index, and the simulation of the optical properties. They are presented in the following.
5.1. Calculation of porous silicon refractive index
PSi is a composite medium with a pore size much smaller than the wavelength of light. Hence, the dielectric response can be described through an effective dielectric function. A complete review of the different isotropic and anisotropic models used for the calculation of PSi refractive index has recently been published (Kochergin & Föll, 2009). In the isotropic approximation, the main models used for the calculation of the effective dielectric function are the Bruggeman and Landau Lifshitz Looyenga (LLL) effective medium approximations (EMA) that can be defined by the following expressions (Bruggeman, 1935; Looyenga, 1965):
where fi and εi are the volume fraction and the complex dielectric function of material i, respectively. The refractive index of materials is related to the permittivity ε with ε = n2. The refractive indices of Si and SiO2 can be obtained from the Palik handbook (Palik, 1998). As the materials are used in their transparency domain, the variations of their refractive indices with the wavelength are deduced from a Cauchy law, using the parameters given in table 1:
n=A+Bλ2+Cλ4
A
B
C
Si
3.4227
0.1104
0.041
SiO2
1.4213
0.0856
-0.0735
Table 1.
Cauchy law and values of the Cauchy coefficients used for the modelling.
In order to consider absorption of light in the doped silicon substrate, variations of the refractive index induced by free carriers absorption have to be taken into account. The relation proposed by Soref is used (Soref & Bennett, 1987), which requires calculation of the electron and holes mobilities depending on substrate doping (Sedra & Smith, 1997).
The models presented above have been implemented to fit experimental data, in particular the reflectivity measurements performed on PSi layers. As an example, the reflectivity spectra of a PSi monolayer before and after an oxidation step are plotted on fig. 7. The parameters of the Bruggeman and LLL models and the thickness of the PSi monolayer are obtained using a Levenberg Marquardt nonlinear fitting method (Press et al., 1992). The results obtained using the Bruggeman and LLL models reproduce well the experimental indices deduced from reflectivity measurements. For this particular sample, the PSi layer was found to have an initial porosity of 70% and 73%, respectively, and a thickness of 4.735 and 4.741 μm, respectively, for the Bruggeman and LLL models. Both models gave a silica fraction of 11% after oxidation. Hence, the fitted parameters are very close for both models, with a relative variation below 5%.
Figure 7.
Evolution of the reflectivity of a PSi monolayer before (dash) and after (straight) oxidation step. The experimental data has been fitted with the Bruggeman and LLL models.
In the following sections, the refractive indices will be determined using the LLL model. Fitting all experimental data using the LLL model, we could evaluate that the volume fractions of silica after oxidation correspond to the formation of a layer having a thickness of 1 nm on the internal PSi walls, for both porosities considered (35% and 80%). This is consistent with the experimental calibrations of the oxidation process. Similarly, the volume fractions of silane molecules deduced from the experimental spectra after silanization are equivalent to the formation of dense layers with refractive index 1.4 and thickness around 1.7 nm covering the internal PSi walls. This layer thickness is similar for both porosities and consistent with the developed length of the silane molecules used (~ 1.7 nm).
5.1. Simulation of optical properties
Numerical modelling is a major concern for the study of PC structures. Along the years, two main approaches have emerged: the plane wave expansion (PWE) and the finite difference in the time domain (FDTD) method.
The PWE method relies on the translation symmetry of the PC structure. The method assumes a time harmonic evolution of the electromagnetic fields. In this case, the Maxwell equations lead to the following general Helmoltz equation:
∇→×(1εr(r→)∇→×H→(r→))=(ωc)2H→(r→)E2
where H stands for the magnetic field, ω the pulsation and εr is the relative dielectric permittivity.
This is an eigenvalue problem, which can be solved using a Fourier expansion along the vectors of the reciprocal lattice. It leads to the dispersion relation ω = ω(k) where k(kx,ky,kz) is the light wave vector. This approach enables a very efficient calculation of the band diagram, giving information on photonic band gaps, group and phase velocity… of the infinite periodic structure. However, this useful approach suffers from some limitations. In its common formulation, it could not easily handle losses (lossy material, leaky modes…). In the following sections, a free software package is used, MIT Photonic Bands (MPB) (Johnson & Joannopoulos, 2001).
When it comes to real finite devices, the FDTD method is more suited. This method relies on the discretization in time and space of the Maxwell equations (Taflove & Hagness, 2005):
∂E→∂t=1ε∇×H→and∂H→∂t=−1μ∇×E→E3
where E and H stand for the electric and magnetic field, respectively, and ε and μ for the dielectric and magnetic permittivity, respectively.
The numerical experiments generally consist in sending an electromagnetic pulse onto the structure and to monitor its response with time. A single simulation run is necessary to get the frequency response thanks to the Fourier transform of the time response. It gives access to the spectral response of the system (transmission, reflection). The ability of FDTD to solve open problems is very useful for the study of microcavities and leaky modes. It gives access to the quality factor (Q factor = λ/Δλ) of resonances. Moreover, an electromagnetic field map at a given frequency could be easily obtained thanks to the discrete Fourier transform. As this method has achieved its full maturity, it can handle dispersive and lossy materials, non-uniform mesh, non-linear effects… Another interesting development is the implementation of periodic boundary conditions which enable the study of infinite PCs. Compared to the PWE, the FDTD method is less efficient; however, it allows for the study of leaky modes (modes above the light line, i.e. in the free-state continuum). The FDTD method also requires a lot of computing resources which are now available, thanks to ever evolving microprocessor power, and it can be by nature easily parallelized.
6. Performance study of photonic-crystal-based biosensors
In this section, a performance study of the two PC-based biosensors is discussed, using the tools and methods presented above. Both devices are considered for use in the infra-red range at around 1300-1500 nm wavelength where absorption losses in the material can be neglected. In this case, the main source of losses in PSi devices is expected to be scattering at the interface of the silicon nanocrystallites (Ferrand & Romestain, 2000). Experimental measurements show that the losses are only a few cm-1 in this wavelength range and should not alter significantly the sensor response. Therefore, we expect our theoretical predictions to be in good agreement with experimental results.
6.1. Surface-wave biosensor
The very high sensitivity of the SW sensor in the 1D – i.e., unpatterned – configuration has been demonstrated both theoretically and experimentally. In particular, we have observed angular variations as large as 20 after grafting of amine molecules inside the PSi device (Guillermain et al., 2007). In further studies, much smaller amounts of biomolecules were considered, in order to evaluate the limit of detection of the biosensor. It was demonstrated that convenient lateral patterning could enhance the sensitivity of the biosensor by an order of magnitude (Jamois et al., 2010a). In these previous studies, we focussed on SW sensors having a high-index surface layer with porosity 35%. Such porosity enables to reach very high sensitivities due to very large PSi internal surface. However, due to the small pore size (< 10 nm) sensing is limited to small biomolecules. In the following, we consider the case of SW sensors having a surface layer with larger porosity 55%, which might yield a slightly lower sensitivity due to smaller PSi internal surface, but enables sensing of larger molecules.
The devices consist of a multilayer with period a and standard porosities P1 = 80% and P2 = 35%, respectively, with corresponding refractive indices n1 = 1.4 and n2 = 2.5 deduced from the LLL model. The multilayer is terminated by a surface layer with porosity Psurf = 55% and refractive index 2.0. Fig. 8 shows the band diagram of the 1D PC for the propagation direction parallel to the surface. As the 1D PC is homogeneous in the direction of propagation, the bands of the 1D structure shown in fig. 8 are continuous. However, the continuity of the bands can be broken by introducing a periodic perturbation. If a periodic pattern is introduced in the direction of propagation, bands are back-folded at the edge of the lateral Brillouin zone – for wave vectors k = π/a – resulting in local band flattening, i.e., a strong decrease of light velocity. After careful optimization of both the multilayer and the array of air slits, a 2D structure was obtained with a PBG large enough to assure a good confinement of the SW. The optimized parameters of the resulting 2D PC are thicknesses d1 = d2 = 0.5a for the multilayer, and w = 0.8a and a’ = 1.2a for the width and period of the air slits, respectively. For a good comparison of the sensor performances, the layer thicknesses are the same for the 1D sensor as for the 2D device. Because the surface mode position within the PBG is highly sensitive to the thickness of the surface layer (Guillermain et al., 2006), optimization of the surface layer thickness has also been necessary to position the SW in the middle of the PBG and thus provide a good light confinement within the surface layer. The optimized thickness of the surface layer is h = 0.4a for both 1D and 2D devices. Fig. 8 shows the band structures for the optimized 1D and 2D SW devices.
Figure 8.
Simulated band structures (MPB) of the SW sensor in air environment for the unpatterned (1D) and patterned (2D) configurations.
As plane-wave simulations consider a semi-infinite structure that is not experimentally achievable, periodic FDTD simulations were also performed to evaluate the performances of more realistic devices. Considering a multilayer consisting of 6 periods and varying the depth of the air slits, it could be verified that the optical properties of the device do not vary significantly with an increase of the slits depth, provided that the air slits are at least 3 multilayer periods deep. Hence, our band structure calculations can well describe the expected device performances, if the depth of the patterns in the experimental 2D sensor reaches 3 multilayer periods.
In order to demonstrate the high device sensitivity, a comparative study of the optical response in the 1D and the 2D cases has been performed in air environment, considering as an initial state a slightly oxidized porous structure (~ 1 nm SiO2) and varying the amount of molecules grafted onto the pore walls. Note that similar results would be obtained in the case of specific biomolecular recognition, provided that the initial refractive index of PSi is adjusted to take into account biochemical functionalization. Moreover, we consider the limiting case where molecule grafting is restricted to the surface layer in order to take into account the inhomogeneous infiltration of liquids and biomolecules inside meso-PSi, which is the largest close to the surface and decreases in the depth of the multilayer, as was demonstrated using labelled proteins (De Stefano & D’Auria, 2007). We should point out that this restriction is underestimating the response of the biosensors.
The shift in the band structure induced by the grafting of 2.5%biomolecules inside the PSi is presented in fig. 9 for both 1D and 2D devices. It can be seen that the much flatter surface band of the 2D sensor leads to much larger variations in wave vector and in resulting coupling angle. In the presence of the biomolecules, the shift in coupling angle is 0.7 for the unpatterned device and as large as 4.0 for the patterned sensor. This corresponds to an increase in sensitivity of the 2D device by a factor 6 compared to the 1D case.
Figure 9.
Optical response of the surface wave sensor to the grafting of 2.5% biomolecules in air environment for the unpatterned (1D) and patterned (2D) configurations.
The variation in coupling angle and in refractive index depending on the amount of biomolecules is presented in fig. 10 for the 2D biosensor. For a better understanding of the amount of biomolecules infiltrated inside the pores, it is also expressed as the equivalent thickness dbio of a dense monolayer having the same volume and homogeneously coating the internal surface of the pores. This formalism has already been used in other studies of photonic sensors based on PSi, and has proven to yield good agreement between theoretical predictions and experimental results (Ouyang et al., 2006). As can be seen in fig. 10a, a variation in coupling angle as large as 13.5 is expected for the grafting of a dense monolayer of biomolecules with thickness 1.7, which corresponds to the case of our silanization process. A much smaller amount of molecules of 0.1% – equivalent to a dense layer with thickness 0.01 nm – would still induce a variation in coupling angle of 1 , with a corresponding variation in refractive index of 6x10-4. Considering that high-performance SPR setups can detect angular variations as small as 0.001 , we can conclude that the limit of detection of the SW sensor is very low.
Figure 10.
Simulated optical response (MPB) of the SW sensor in air environment as a function of the amount of detected biomolecules: (a) for large amounts, and (b) for smaller amounts. The optical response is expressed both as a shift in coupling angle (Δθ) and as the corresponding refractive index variation in the top layer (Δn). The amount of biomolecules is given as a volume fraction inside the PSi (fbio) and as an equivalent thickness (dbio). The blue dashed line indicates the expected device response to silane grafting.
6.2. Planar photonic-crystal biosensor
The optical response of the planar PC observed at normal incidence shows the superposition between interferences occurring inside the PSi layers and the excited Fano resonances. In order to maximize the variation of reflection induced by biosensing events, the structure has to be optimized to position the resonance in a zero of reflectivity corresponding to destructive interferences within the PSi layers. This way, the reflected signal at resonance can be switched between 0% and 100%. The device optimization was performed combining plane-wave and FDTD simulations for the TE polarization where the electric field is parallel to the slits (Jamois et al., 2010b). After optimization, the band structure presented in fig. 11a was obtained, yielding a Fano resonance with very sharp features at a relative frequency a/λ = 0.66 very close to the Γ point, where it can be excited at normal incidence. The Q factor of the resonance can be as high as 1200 for the optimized 1D PC with top layer thickness h = 0.75a and trench width w = 0.4a. Note that the Q factor is very sensitive to the thickness of the top PSi layer: increasing or decreasing the thickness by only 50 nm results in a reduction of the Q factor by several hundred. As our fabrication process enables a very good control of the layer thicknesses, the sensitivity of the Q factor should not have a significant impact on the device performances. The Q factor also strongly varies with the filling factor, i.e., the relative width of the air slits, which means that the experimental fabrication process should be carefully calibrated to obtain the desired slit widths.
In order to evaluate the performance of the device for biosensing, a similar study was performed as in the case of the SW sensor, considering as an initial state a slightly oxidized porous structure (~ 1 nm SiO2) and varying the amount of molecules grafted onto the pore walls. Fig. 11b shows the shift of the resonance depending on the amount of biomolecules. Due to the finesse of the resonance, the presence of only 0.35% biomolecules leads to a shift of the resonance large enough to induce a dramatic decrease in reflectivity from 100% (green curve) down to 32% (red curve). The wavelength variation of the resonance depending on the amount of biomolecules is presented in fig. 12a-b, where the amount of biomolecules is
Figure 11.
a) Band structure of the planar photonic crystal device (MPB simulation). The resonance of interest for biosensing is marked by a purple circle. (b) Reflectivity behaviour showing the resonance shift depending on the amount of biomolecules (FDTD simulation).
again expressed both as a volume fraction fbio and as an equivalent thickness dbio. The corresponding refractive index variation of the top PSi layer is also shown. As this study is performed in air environment, the wavelength variation is determined for an initial resonance centred at 1500 nm. Fig. 12a highlights the very large sensitivity of the device; indeed, in the case of grafting of a dense monolayer of silane molecules with a length of 1.7 nm, the expected shift of the resonance is larger than 50 nm. Fig. 12b demonstrates that smaller amounts of biomolecules can be well detected as well, since the grafting of 0.35% of molecules – equivalent to a dense monolayer with only 0.02 nm thickness – would induce a wavelength shift larger than 1 nm, which is in good agreement with fig. 11b. The induced refractive index variation for this small amount of biomolecules would be below 2x10-3.
In order to evaluate the performances of the sensor for in-situ measurements, the same study has been performed in aqueous environment. In this case, all the pores of the PSi layers as well as the trenches are completely filled with water. The presence of water inside the pores induces an increase of the oxidized PSi refractive index to 2.52 and 1.63, respectively, for the top layer and the substrate. Hence, the index contrasts remain quite large between the layers of different porosities, as well as between the PSi and the water-filled slits. After a new optimization of the photonic crystal to take into account the new index configuration, a similar Fano resonance was found to yield a Q factor above 1000 if the thickness of the top layer is adjusted to 0.8a. This means that the presence of water does not dramatically alter the device performances. Fig. 12c-d shows the optical response of the sensor in aqueous environment with varying amount of biomolecules. For a better comparison with the results obtained in air environment, the wavelength shifts have been calculated for a resonance centred at 1500 nm. When using the device at shorter wavelength (e.g., at 1300 nm where water absorption is strongly reduced) the wavelength shift of the resonance is correspondingly slightly smaller. Due to the lower refractive index difference between biomolecules and water (Δn < 0.1) than between biomolecules and air (Δn ~ 1.4), it is expected that the same volume of molecules induces a lower optical response in aqueous environment. In this case, silane grafting shown in fig. 12c would induce a shift of the
Figure 12.
Simulated optical response (MPB) of the planar photonic crystal biosensor in air and aqueous environment, respectively: (a), (c) for large amounts of biomolecules, and (b), (d) for smaller amounts. The optical response is expressed both in wavelength shift (Δλ) and in corresponding refractive index variation in the top layer (Δn). The amount of biomolecules is given as a volume fraction (fbio) and as an equivalent thickness (dbio). The blue dashed line indicates the expected device response to silane grafting.
resonance by 7.5 nm, which corresponds to a decrease in sensitivity by a factor 7 compared to the sensor in air environment. However, we can see in fig. 12d that very small amounts of biomolecules can still be detected, as the grafting of 1% of biomolecules, equivalent to a dense monolayer with 0.06 nm thickness, would induce a wavelength shift of 0.5 nm.
In order to study the experimental response of the biosensor, the process discussed in section 4 was used to realize devices similar to the one shown in fig 5b. The fabricated devices were then functionalized and their optical properties were characterized by reflectivity measurements at each main functionalization step. The optical setup used for the reflectivity measurements, presented in fig. 13a, is equipped with a wide band 1200-1600 nm laser diode source and an InGaAs detector. Light is focussed on the 100 μm x 100 μm size device via a microscope objective. Nano-positioning of the sample is achieved via an XYZ piezoelectric table and is monitored with a visualization camera.
The optical response of the device is presented in fig. 13b. The green spectrum shows the reflectivity of the device after oxidation. The oscillations in reflectivity due to the interferences in the PSi substrate are clearly visible. Superimposed to these oscillations, 2
Figure 13.
a) Schematic view of the optical setup. (b) Reflectivity measurements of the planar PC device, after oxidation (green curve) and after subsequent silanization (red curve).
main resonances can be seen, the first one around 1280 nm and a sharper resonance at 1530 nm. This second resonance is the Fano resonance of interest for biosensing. After silanization, the same device has been characterized again and the red spectrum has been obtained. Comparing the two spectra, it can be observed that the interference fringes have shifted, indicating a change in refractive index of the PSi layer and successful silane grafting. Moreover, the second resonance that was initially at 1530 nm shows a strong 52 nm red shift, which is in perfect agreement with the simulated expectations discussed in fig. 12.
After immobilization of DNA probes on the silanized PSi surface, the devices show strong 20 nm blue shifts, which are a signature of PSi corrosion due to remaining Si-H bonds (Steinem et al., 2004). Although the amount of Si-H and Si-OH bonds is very low – almost invisible on FTIR spectra – their presence is sufficient to induce a damage of the PSi structure with the resulting blue shift, and to prevent any quantitative measurement of the immobilized DNA molecules. Hence, both our oxidation process and the surface capping by the silane molecules should be further improved to completely eliminate the Si-H bonds or to prevent access from the water molecules to these H-bonds.
7. Conclusion
In this chapter, new concepts for meso-PSi integrated optical biosensors based on photonic crystals have been presented, as well as the study of their performances.
The first biosensor is based on the excitation of SW at the surface of a PC device. Such devices yield very high sensitivity that can be further enhanced by the introduction of lateral patterning. We demonstrated a gain in sensitivity by a factor 6 between the 1D and 2D biosensors. Another great property of this biosensor is the possibility to adjust the porosity of the surface layer depending on the size of the target biomolecules. One disadvantage of the SW device is that prism coupling requires large optical setups that are not convenient for mass applications. It also requires large device areas and is not compatible with on-chip multiple parallel sensing. These limitations can be overcome if the prism is replaced, e.g., by a grating and if a detection principle similar to SPRI setups is used. The other limitation of the SW sensor in its 2D configuration is a quite challenging technological realization due to the depth of the slits that have to be patterned into the PSi multilayer. New processes are currently been developed to enable the fabrication and experimental study of these sensors.
The second biosensor is based on the excitation of Fano resonances in planar PCs at normal incidence. Such devices require simpler optical setups, they are very compact and can be directly integrated into optical microchips, enabling for multiple parallel sensing. They yield high sensitivity and their experimental realization is less challenging than in the case of SW devices. We demonstrated perfect agreement between the theoretical and experimental performances and shift of the resonance wavelength as large as 52 nm after grafting of a silane monolayer. Because the porosity of the top layer cannot be too large in order to yield good optical properties, these sensors are restricted to the detection of small biomolecules. Further optimization of the sensor design will help to overcome this limitation.
Therefore, PCs in PSi are a very promising route to realize high performance biosensors that can be fully integrated into optical microchips and used for in-situ analysis. As both the experimental realization and the theoretical design of the devices are still at the focus of intensive research, new exciting developments will certainly occur in a near future.
Acknowledgments
The experimental work is performed at the technological platform Nanolyon. R. Mazurczyk, P. Crémillieu, C. Seassal, A. Sabac and J.-L. Leclercq are kindly acknowledged for fruitful discussions on fabrication techniques and technical support. We are also very grateful to C. Martinet, G. Grenet, C. Botella, N. Blanchard, P. Regreny and D. Leonard for their help on physico-chemical characterization of PSi.Financial support by the French ANR in the framework of the research project BiP BiP (JC09_440814), and the INSA-Lyon in the framework of a BQR project, as well as the CSC for PhD stipend funding are acknowledged.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/16431.pdf",chapterXML:"https://mts.intechopen.com/source/xml/16431.xml",downloadPdfUrl:"/chapter/pdf-download/16431",previewPdfUrl:"/chapter/pdf-preview/16431",totalDownloads:3268,totalViews:312,totalCrossrefCites:0,totalDimensionsCites:6,totalAltmetricsMentions:0,impactScore:2,impactScorePercentile:81,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"October 19th 2010",dateReviewed:"March 4th 2011",datePrePublished:null,datePublished:"July 18th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/16431",risUrl:"/chapter/ris/16431",book:{id:"147",slug:"biosensors-emerging-materials-and-applications"},signatures:"Cheng Li, Emmanuel Gerelli, Regis Orobtchouk, Taha Benyattou, Ali Belarouci, Yann Chevolot, Virginie Monnier, Eliane Souteyrand and Cecile Jamois",authors:[{id:"27544",title:"Dr.",name:"Cecile",middleName:null,surname:"Jamois",fullName:"Cecile Jamois",slug:"cecile-jamois",email:"cecile.jamois@insa-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Institut National des Sciences Appliquées de Lyon",institutionURL:null,country:{name:"France"}}},{id:"35813",title:"Dr.",name:"Cheng",middleName:null,surname:"Li",fullName:"Cheng Li",slug:"cheng-li",email:"cheng.li1@insa-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"35814",title:"Mr.",name:"Emmanuel",middleName:null,surname:"Gerelli",fullName:"Emmanuel Gerelli",slug:"emmanuel-gerelli",email:"emmanuel.gerelli@insa-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"35815",title:"Dr.",name:"Regis",middleName:null,surname:"Orobtchouk",fullName:"Regis Orobtchouk",slug:"regis-orobtchouk",email:"regis.orobtchouk@insa-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"35816",title:"Dr.",name:"Taha",middleName:null,surname:"Benyattou",fullName:"Taha Benyattou",slug:"taha-benyattou",email:"taha.benyattou@insa-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"35817",title:"Dr.",name:"Ali",middleName:null,surname:"Belarouci",fullName:"Ali Belarouci",slug:"ali-belarouci",email:"Ali.Belarouci@ec-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"35818",title:"Dr.",name:"Yann",middleName:null,surname:"Chevolot",fullName:"Yann Chevolot",slug:"yann-chevolot",email:"Yann.Chevolot@ec-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"35819",title:"Dr.",name:"Virginie",middleName:null,surname:"Monnier",fullName:"Virginie Monnier",slug:"virginie-monnier",email:"Virginie.Monnier@ec-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"35820",title:"Dr.",name:"Eliane",middleName:null,surname:"Souteyrand",fullName:"Eliane Souteyrand",slug:"eliane-souteyrand",email:"Eliane.Souteyrand@ec-lyon.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction ",level:"1"},{id:"sec_2",title:"2. Biosensors based on porous silicon",level:"1"},{id:"sec_3",title:"3. Novel photonic-crystal-based biosensors",level:"1"},{id:"sec_3_2",title:"3.1. Surface-wave biosensor",level:"2"},{id:"sec_4_2",title:"3.2. Planar photonic-crystal biosensor",level:"2"},{id:"sec_6",title:"4. Experimental realization",level:"1"},{id:"sec_6_2",title:"4.1. Porous silicon anodization",level:"2"},{id:"sec_7_2",title:"4.2. Porous silicon patterning",level:"2"},{id:"sec_8_2",title:"4.3. Porous silicon functionalization for DNA sensing",level:"2"},{id:"sec_10",title:"5. Modeling of optical properties",level:"1"},{id:"sec_10_2",title:"5.1. Calculation of porous silicon refractive index",level:"2"},{id:"sec_11_2",title:"5.1. Simulation of optical properties",level:"2"},{id:"sec_13",title:"6. Performance study of photonic-crystal-based biosensors",level:"1"},{id:"sec_13_2",title:"6.1. Surface-wave biosensor",level:"2"},{id:"sec_14_2",title:"6.2. 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R.\n\t\t\t\t\t2008 Catalyzed oxidative corrosion of porous silicon used as an optical transducer for ligand-receptor interactions. ChemBioChem, 9\n\t\t\t\t\t11761186\n\t\t\t'},{id:"B75",body:'ZhangJ.PourceauG.MeyerA.VidalS.PralyJ.P.SouteyrandE.VasseurJ.J.MorvanF.ChevolotY.\n\t\t\t\t\t2009a\n\t\t\t\t\tDNA-directed immobilisation of glycomimetics for glycoarrays application: Comparison with covalent immobilisation, and development of an on-chip IC50 measurement assay.\n\t\t\t\t\tBiosensors and Bioelectronics, 24\n\t\t\t\t\t8\n\t\t\t\t\t2515\n\t\t\t\t\t0956-5663'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Cécile Jamois",address:null,affiliation:'
Institut des Nanotechnologies de Lyon (INL), CNRS UMR 5270, INSA-Lyon, France
School of Physics, Alagappa University, Karaikudi, Tamil Nadu, Université de Lyon, France
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1. Introduction
Kisspeptins are a family of neuropeptides with diverse functions in humans. They are cleaved from a precursor peptide encoded by the KISS-1 gene, which was originally identified in melanoma cells as a metastasis suppressor gene [1]. Expression of KISS-1 has subsequently been identified in many other cell lines, including those of the placenta, ovaries, and testes [2]. It is now known that kisspeptin plays a critical role in reproduction and fertility [3]. Kisspeptin is believed to regulate the secretion of gonadotropin-releasing hormone (GnRH) by integrating central and peripheral signals [4]. During the menstrual cycle, gonadal sex steroid concentrations impact the secretion of GnRH from neurons located in the hypothalamus. It is hypothesized that kisspeptin mediates this hypothalamic feedback because 1) GnRH neurons lack gonadal sex steroid receptors but some express kisspeptin receptors [5, 6, 7] and 2) kisspeptin neurons express sex steroid receptors [8, 9]. This review will focus on the role of kisspeptins throughout the menstrual cycle and their potential use as a biomarker of viable pregnancy.
2. Kisspeptin in the follicular phase and periovulation
Kisspeptin neurons are primarily located in the preoptic area and hypothalamic arcuate nucleus and function as upstream regulators of GnRH neurons [10]. In both of these anatomic locations, serum estrogen and progesterone concentrations have been shown to regulate kisspeptin-mediated GnRH secretion [11]. During the early follicular phase of the menstrual cycle, estrogen exerts negative feedback on GnRH stimulation of luteinizing hormone (LH) secretion. As the follicular phase progresses, rising estrogen levels result in pulsatile secretion of GnRH, which then stimulates the pulsatile release of follicle-stimulating hormone (FSH) and LH [10]. This pulsatile secretion pattern is likely mediated by kisspeptin through regulation of GnRH neurons. Involvement of kisspeptin in this regulatory pathway is suspected because GnRH neurons lack estrogen and progesterone receptors, and thus cannot directly respond to serum sex steroid concentrations [12, 13]. The absence of a direct biochemical connection between the gonads and hypothalamus suggests the presence of an intermediary signal. This “missing link” is thought to be kisspeptin neurons, which express estrogen receptors and secrete a ligand that can bind to GnRH [12].
During the early follicular phase when follicles are underdeveloped, kisspeptin levels are low [4, 14]. A study by Zhai et al. showed that kisspeptin levels sharply increase when the dominant follicle reaches 1.2 cm in diameter [14]. Kisspeptin levels during the periovulatory period are then high [4, 14, 15], and may have potential in predicting development of the dominant ovarian follicle [14]. A study by Dhillo et al. demonstrated that administration of exogenous kisspeptin to healthy women results in increased gonadotropin secretion; this response is most potent during the preovulatory phase [16].
A study by Meczekalski et al. demonstrated that kisspeptin and LH are co-secreted (i.e. each kisspeptin pulse is accompanied by a pituitary LH pulse in response to a hypothalamic GnRH pulse) [11]. Another study demonstrated that blockade of the kisspeptin receptor (GPR54) resulted in blockade of pulsatile LH secretion [17]. There is also topographical evidence of the connection between GnRH and kisspeptin neurons – in several species, it has been shown that GnRH neuronal axons extend from the arcuate nucleus, where kisspeptin neurons are located, to the median eminence, where GnRH is secreted [12]. Human studies have not reproducibly demonstrated this neuroanatomy for all GnRH neurons, which may suggest that kisspeptin neuronal connections in humans are more complex [11, 18].
3. Kisspeptin in ovulation
At mid-cycle, estrogen secreted by the preovulatory follicle eventually triggers GnRH neurons to transition from pulsatile GnRH secretion to sustained secretion. The mechanism by which estrogen transforms from a negative to positive feedback signal on the hypothalamus still remains unclear. Estrogen binds to the ERα receptor on kisspeptin neurons in the arcuate nucleus, inhibiting kisspeptin secretion and subsequent GnRH secretion [15]. In the anteroventral periventricular nucleus, estrogen binds kisspeptin ERα receptors and exerts positive feedback, which ultimately initiates the LH surge associated with ovulation.
The sustained secretion of high concentrations of GnRH (GnRH surge) occurs for over 24 hours and triggers the pituitary gland to secrete high levels of LH (LH surge) [19]. The LH surge is what ultimately triggers ovulation [7]. The LH surge is also the target of at-home ovulation predictor kits [14]. This cascade of hormone surges is thought to be primarily regulated by kisspeptin; in fact, kisspeptin is the most potent activator of GnRH neurons discovered to date [5]. It is suspected that rising estrogen levels during the follicular phase stimulate kisspeptin neurons, which then activate GnRH neurons to initiate the GnRH surge [7]. In contrast, administration of a monoclonal antibody that blocks kisspeptin has been shown to prevent ovulation in rat models [20].
It is postulated that kisspeptin could be useful as a biomarker of the periovulatory/ovulatory phase [14]. This would be clinically useful because kisspeptin surges prior to LH and therefore could predict the time of ovulation before it happens (rather than as it happens). The target of most ovulation prediction kits is LH, which surges at the time of ovulation. According to Zhai et al., the probability of ovulation is increased when kisspeptin surges on the 11th day and LH surges on the 14th day [14]. In comparison, a study by Goto et al. showed that administration of a kisspeptin antagonist resulted in shrinkage of ovarian follicles and delayed ovulation [21].
4. Kisspeptin in the luteal phase and implantation
Kisspeptin is not only expressed in the central nervous system – it also performs peripheral functions. Expression of kisspeptin and its receptor KISS-1 has been demonstrated in the human ovary, fallopian tube, uterus, and placenta [22]. It is thought that kisspeptin primarily functions in the hypothalamus, but also interacts between the signaling pathways of the central and peripheral reproductive systems [23]. In fact, several studies have supported the idea that kisspeptin exerts direct effects on ovarian tissue via ovarian kisspeptin receptors [24, 25, 26].
A number of studies have demonstrated that kisspeptin is expressed at the maternal-fetal interface of many species, including humans [27]. In the human uterus, kisspeptin is expressed in the endometrial epithelial and stromal cells, but not in the myometrium [28]. In the early placenta, kisspeptin is initially produced by villous cytotrophoblast cells, then villous syncytiotrophoblast cells and the placental bed [29, 30]. As pregnancy progresses, placental production of kisspeptin declines [31, 32].
Kisspeptin expression in the endometrium is absent during the proliferative and early secretory phases but becomes abundant during the late secretory phase [27, 33]. This indicates a potential role of kisspeptin in the preparation of endometrial tissue for implantation. Kisspeptin knockout mice exhibit thin, weak uteri with almost no endometrial glands, suggesting kisspeptin is an important regulator of normal endometrial development [34]. Kisspeptin may also act as a mediator that facilitates implantation of the growing embryo to the uterine wall. It has been shown that exogenous kisspeptin administration strengthens adhesion of kisspeptin-expressing trophoblast cells to collagen present in uterine tissue [34]. Immediately after implantation, kisspeptin levels are known to rise; this suggests involvement of kisspeptin during the decidualization process [35]. A study by Wu et al. demonstrated a dose-dependent relationship between kisspeptin expression and inhibition of cell invasion/migration in human decidualized endometrial cells [29]. In contrast, a kisspeptin antagonist called kisspeptin 234 stimulates the process of decidual invasion and migration [29]. Similarly, when small interfering RNAs that antagonize kisspeptin are introduced, stromal decidualization is impaired [35]. In a study by Calder et al., ablation of the KISS-1 gene and subsequent absence of kisspeptin expression resulted in infertile mice [36]. Even in mice that received rescue gonadotropins and estradiol, which restored ovulation, the mice embryos could not implant in the mice that lacked KISS-1. These embryos were, however, able to implant in wildtype mice [36].
Kisspeptin was originally identified as a suppressor of cancer metastasis; its function in the regulation of cellular proliferation and growth is also integral to the process of placentation. The early placenta expresses high levels of kisspeptin, perhaps to tame the invasive and migratory capability of trophoblasts [32]. Kisspeptin decreases the activity of collagenases, matrix metalloproteinases, and vascular endothelial growth factor, which are all signaling proteins involved in trophoblast proliferation [31, 37]. Kisspeptin also supports the adhesion of extravillous trophoblasts to the endometrium, which inhibits migration [38]. This careful balance between invasion and the prevention of invasion is essential to the placentation process as well as the appropriate remodeling of the maternal uterine wall [34]. As the placenta develops throughout pregnancy, it exhibits a pattern of kisspeptin expression that follows a circadian rhythm [39]. The term placenta demonstrates kisspeptin surges at 0400 and 1200 daily. This rhythm correlates with circadian expression of other proteins involved in placental physiology, including TNFα, melatonin, and oxytocin [39].
5. Kisspeptin in pregnancy
Maternal kisspeptin levels rise dramatically during pregnancy, then return to normal within 15 days of delivery [28]. Unlike β-hCG, kisspeptin levels rise steadily and do not plateau [40]. It is thought that the primary source of maternal kisspeptin is placental tissue [27], and that maternal kisspeptin levels reflect the volume of viable placental tissue [41]. Kisspeptin may be useful as a biomarker of pregnancy due to its association with placental invasion and apoptosis [42]. It also has potential utility as a biomarker of miscarriage.
Spontaneous abortion (SAB) is a common experience, seen in 10–20% of clinically recognized pregnancies [43]. A study by Jayasena et al. showed that maternal plasma kisspeptin is significantly lower in women with early pregnancies who later develop SAB compared to women who have a viable intrauterine pregnancy (IUP) [44]. Maternal kisspeptin levels also had higher diagnostic performance than β-hCG in detecting SAB [44]. Wu et al. demonstrated that women with recurrent SAB have decreased decidual kisspeptin expression compared to women with IUP [45]. Kavvasoglu also showed decreased maternal kisspeptin levels in women with SAB compared to healthy IUPs [46]. Sullivan et al. validated a serum kisspeptin-54 assay as well as confirmed that maternal kisspeptin levels are positively correlated with fetal gestational age and pregnancy viability [40].
There is currently no established clinical test for early miscarriage; diagnosis relies on serial β-hCG measurements and correlation with ultrasound. This requires multiple maternal encounters with the healthcare system, a prolonged timeframe, and can involve considerable distress of the patient and partner. Jayasena et al. describes the current diagnostic pathway for establishing fetal viability as having limited clinical utility due to delay and a high degree of uncertainty [44]. Thus, there is interest in establishing a more accurate and streamlined diagnostic marker of viable IUP vs. SAB.
Kisspeptin has been shown to be massively downregulated in the case of ectopic pregnancy [47]. Ectopic pregnancy occurs when a fertilized ovum implants and develops outside the uterine cavity. Similarly to SAB, ectopic pregnancy is currently diagnosed by serial β-hCG measurements in correlation with ultrasound. Definitive diagnosis may require direct visualization via laparoscopy [48]. A study by Romero-Ruiz et al. explored the roll of kisspeptin in individuals with ectopic pregnancy. They found that maternal circulating kisspeptins gradually increased during the first trimester of pregnancy in healthy controls. However, in those with ectopic pregnancy, kisspeptin levels were suppressed. The study correlated these results to levels of microRNAs (miRNA) (small noncoding RNAs that can modulate gene and protein expression). In particular, miR-324-3p is known to inhibit kisspeptin function. Romero-Ruiz et al. found that in ectopic pregnancies, miR-324-3p was significantly increased in placental tissue (though maternal circulating levels were low). This finding suggests defective export of the miRNA from its embryonic/placental source in ectopic pregnancy, which may further contribute to the local suppression of kisspeptin. The authors suggested that correlation of maternal miR-324-3p with kisspeptin and β-hCG levels could provide a better modality for timely diagnosis of ectopic pregnancy, especially considering the stability of miRNA in maternal serum [46].
Kisspeptin could also have diagnostic utility in identifying women at risk of preeclampsia. A study by Qaio showed that the placentas of term preeclamptic pregnancies express significantly lower kisspeptin levels compared to healthy pregnancies [49]. These findings were reproduced by Farina et al., which demonstrated lower KISS-1 expression in preeclamptic patients compared to healthy pregnant patients [50]. The study also suggested KISS-1 cell-free mRNA has potential to serve as a predictive biomarker of preeclampsia [50]. Matjila et al. investigated the relationship between maternal kisspeptin levels and placental kisspeptin expression in preeclamptic pregnancies – they found that preeclamptic placentas demonstrated high kisspeptin expression but low maternal kisspeptin levels [30]. It is speculated that elevated kisspeptin expression in diseased placentas may inhibit trophoblast invasion and contribute to the development of preeclampsia [30, 34]. Kisspeptin therefore has potential to offer predictive information about the risk of preeclampsia.
6. Kisspeptin in in vitro fertilization
Because of its apparent role in reproduction and fertility, there is interest in the use of kisspeptin as a tool to aid in assisted reproductive technology. Exogenous kisspeptin has been used to trigger oocyte maturation in women undergoing in vitro fertilization (IVF) with very low rates of ovarian hyperstimulation syndrome (OHSS) [41, 51]. Oocyte maturation is the process during which an oocyte transitions from metaphase I to metaphase II; at this time, it is capable of becoming fertilized [51]. Jayasena et al. demonstrated that a single kisspeptin bolus was capable of producing an LH surge that induced oocyte maturation in women undergoing IVF [41]. This was an important study, as it was the first to label kisspeptin as an effective maturation trigger. 92% of the study participants who received kisspeptin had at least one embryo available for transfer [41]. A study by Owens et al. then demonstrated that when kisspeptin is administered as an oocyte trigger during IVF cycles, granulosa cell gene expression is altered in such a way that increases FSH and LH receptor expression [52]. This altered gene expression is postulated to augment downstream signaling, resulting in increased sex steroid synthesis [52]. In fact, kisspeptin is currently considered to be the most potent stimulator of GnRH secretion [53, 54].
OHSS is considered a serious adverse event during IVF treatment and is typically related to the use of hCG as a trigger for oocyte maturation. This syndrome is characterized by extreme vascular permeability, which can result in pleural effusions, ascites, renal impairment, and in severe cases, death [51]. This vascular permeability is a downstream effect of hCG-mediated release of vascular endothelial growth factor (VEGF) from the ovary [55]. Kisspeptin has been shown to directly inhibit ovarian VEGF production, which significantly decreases the risk of OHSS when used as a trigger for ovulation induction [56]. Moreover, kisspeptin acts to release endogenous GnRH, which triggers an LH surge dependent on the individual’s own GnRH reserves, and is unlikely to excessively or pathologically stimulate the ovaries [57].
7. Kisspeptin in puberty
In addition to its role in pregnancy and fertility, kisspeptin is also implicated in sexual development in humans. The target of the kisspeptin molecule is G-protein coupled receptor 54 (GPR54) [58]. A study by de Roux et al. demonstrated that humans with a defect in the GPR54 gene exhibit isolated hypogonadotrophic hypogonadism, suggesting that kisspeptin is an important regulator of gonadal axis development [59]. This finding was then reproduced by an independent study by Seminara et al., who evaluated a large family with idiopathic hypogonadotrophic hypogonadism and generated GPR54 knockout mice, which failed to undergo adult sexual development and had low serum gonadotropin levels [47]. In contrast, exogenous kisspeptin administration in prepubertal rodents and primates has been shown to induce precocious puberty [60]. Furthermore, Teles et al. describes a female with an activating mutation of GPR54 who exhibited idiopathic central precocious puberty [61].
Kisspeptin is thought to be imperative in all phases of sexual development, beginning in the embryonic phase. During the second trimester of pregnancy, GnRH secretion first occurs and is required for normal testicular development [62]. Aberrant gonadal pathways can result in male infants born with microphallus or cryptorchidism [63]. Kisspeptin is suspected to be crucial in the stimulation of GnRH secretion in both infancy and puberty [62].
8. Conclusion
Kisspeptins have a multitude of regulatory neuroendocrine functions that span the sexual life cycle. Though its mechanisms are not entirely characterized, there is strong evidence supporting its involvement in puberty and development, ovulation, implantation, and pregnancy. Because of their role in these reproductive processes, kisspeptins have potential to be useful as biomarkers in a variety of contexts, such as ovulation prediction and diagnosis of viable IUP. Kisspeptins may also be useful in the advancement of assisted reproductive technology. Continued exploration of kisspeptin function will help to develop and standardize practices that harness its diagnostic and therapeutic potential.
\n',keywords:"kisspeptin, reproduction, fertility, placentation, biomarker",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/77030.pdf",chapterXML:"https://mts.intechopen.com/source/xml/77030.xml",downloadPdfUrl:"/chapter/pdf-download/77030",previewPdfUrl:"/chapter/pdf-preview/77030",totalDownloads:194,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 24th 2021",dateReviewed:"May 18th 2021",datePrePublished:"June 7th 2021",datePublished:"November 17th 2021",dateFinished:"June 3rd 2021",readingETA:"0",abstract:"Kisspeptins are a group of neuropeptides with regulatory functions related to puberty, fertility, and reproduction. They are primarily produced by hypothalamic nuclei and are thought to regulate the activity of neurons that produce gonadotropin-releasing hormone. They are also expressed by placental syncytiotrophoblasts in developing pregnancies and are likely involved in the processes of trophoblast invasion and placentation. Similarly to beta-hCG, kisspeptins are found in maternal plasma during the first trimester of pregnancy and increase proportionately with gestational age. Because of their role in implantation, there is currently interest in the use of kisspeptins as minimally invasive biomarkers. 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Introduction",level:"1"},{id:"sec_2",title:"2. Kisspeptin in the follicular phase and periovulation",level:"1"},{id:"sec_3",title:"3. Kisspeptin in ovulation",level:"1"},{id:"sec_4",title:"4. Kisspeptin in the luteal phase and implantation",level:"1"},{id:"sec_5",title:"5. Kisspeptin in pregnancy",level:"1"},{id:"sec_6",title:"6. Kisspeptin in in vitro fertilization",level:"1"},{id:"sec_7",title:"7. Kisspeptin in puberty",level:"1"},{id:"sec_8",title:"8. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276(37):34631-34636.'},{id:"B2",body:'Horikoshi Y, Matsumoto H, Takatsu Y, Ohtaki T, Kitada C, Usuki S, et al. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. 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Neuroendocrinology. 2014;99(1):33-48.'},{id:"B13",body:'Leonardi CEP, Dias FCF, Adams GP, Araujo ER, Singh J. Kisspeptin induces ovulation in heifers under low plasma progesterone concentrations. Theriogenology. 2020;141:26-34.'},{id:"B14",body:'Zhai J, Ding L, Zhao S, Li W, Sun Y, Su S, et al. Kisspeptin: a new marker for human pre-ovulation. Gynecol Endocrinol. 2017;33(7):560-563.'},{id:"B15",body:'Smith JT, Popa SM, Clifton DK, Hoffman GE, Steiner RA. Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci. 2006;26(25):6687-6694.'},{id:"B16",body:'Dhillo WS, Chaudhri OB, Thompson EL, Murphy KG, Patterson M, Ramachandran R, et al. Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. J Clin Endocrinol Metab. 2007;92(10):3958-3966.'},{id:"B17",body:'Roseweir AK, Kauffman AS, Smith JT, Guerriero KA, Morgan K, Pielecka-Fortuna J, et al. Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J Neurosci. 2009;29(12):3920-3929.'},{id:"B18",body:'Genazzani ADML, BM, Claudia Strucchi, Stefano Luisi1, EC, Bernardi1 F, ARGaFP. Pulsatile secretory characteristics of allopregnanolone, a neuroactive steroid, during the menstrual cycle and in amenorrheic subjects. European Journal of Endocrinology 2002;146:347-356.'},{id:"B19",body:'Caraty A. Nature and bioactivity of gonadotropin-releasing hormone (GnRH) secreted during the GnRH surge. 1995;136(8):3452-3460.'},{id:"B20",body:'Kinoshita M, Tsukamura H, Adachi S, Matsui H, Uenoyama Y, Iwata K, et al. Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats. Endocrinology. 2005;146(10):4431-4436.'},{id:"B21",body:'Goto Y, Endo N, Nagai K, Ohkura S, Wakabayashi Y, Tanaka A, et al. Ovarian and hormonal responses to follicular phase administration of investigational metastin/kisspeptin analog, TAK-683, in goats. Reprod Domest Anim. 2014;49(2):338-342.'},{id:"B22",body:'Cejudo Roman A, Pinto FM, Dorta I, Almeida TA, Hernandez M, Illanes M, et al. Analysis of the expression of neurokinin B, kisspeptin, and their cognate receptors NK3R and KISS1R in the human female genital tract. Fertil Steril. 2012;97(5):1213-1219.'},{id:"B23",body:'Jamil Z, Fatima SS, Arif S, Alam F, Rehman R. Kisspeptin and embryo implantation after ICSI. Reprod Biomed Online. 2017;34(2):147-153.'},{id:"B24",body:'Castellano JM, Tena-Sempere M. Animal modeling of early programming and disruption of pubertal maturation. 2016. p. 87-121.'},{id:"B25",body:'Byri P, Gangineni A, Reddy KR, Raghavender KBP. Effect of kisspeptin on in vitro maturation of sheep oocytes. Vet World. 2017;10(3):276-280.'},{id:"B26",body:'Abbara A, Clarke S, Islam R, Prague JK, Comninos AN, Narayanaswamy S, et al. 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Mol Reprod Dev. 2014;81(1):42-54.'},{id:"B39",body:'de Pedro MA, Moran J, Diaz I, Murias L, Fernandez-Plaza C, Gonzalez C, et al. Circadian Kisspeptin expression in human term placenta. Placenta. 2015;36(11):1337-1339.'},{id:"B40",body:'Sullivan-Pyke C, Haisenleder DJ, Senapati S, Nicolais O, Eisenberg E, Sammel MD, et al. Kisspeptin as a new serum biomarker to discriminate miscarriage from viable intrauterine pregnancy. Fertil Steril. 2018;109(1):137-41.e2.'},{id:"B41",body:'Jayasena CN, Abbara A, Comninos AN, Nijher GM, Christopoulos G, Narayanaswamy S, et al. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. 2014;124(8):3667-3677.'},{id:"B42",body:'Torricelli M, Novembri R, Conti N, De Falco G, De Bonis M, Petraglia F. Correlation with placental kisspeptin in postterm pregnancy and apoptosis. Reprod Sci. 2012;19(10):1133-1137.'},{id:"B43",body:'Ammon Avalos L, Galindo C, Li DK. A systematic review to calculate background miscarriage rates using life table analysis. Birth Defects Res A Clin Mol Teratol. 2012;94(6):417-423.'},{id:"B44",body:'Jayasena CN, Abbara A, Izzi-Engbeaya C, Comninos AN, Harvey RA, Gonzalez Maffe J, et al. Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage. J Clin Endocrinol Metab. 2014;99(12):E2652-E2660.'},{id:"B45",body:'Wu S, Zhang H, Tian J, Liu L, Dong Y, Mao T. Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion. Pathol Res Pract. 2014;210(1):47-54.'},{id:"B46",body:'Kavvasoglu S, Ozkan ZS, Kumbak B, Simsek M, Ilhan N. Association of kisspeptin-10 levels with abortus imminens: A preliminary study. Archives of Gynecology and Obstetrics. 2012;285(3):649-653.'},{id:"B47",body:'Romero-Ruiz A, Avendaño MS, Dominguez F, Lozoya T, Molina-Abril H, Sangiao-Alvarellos S, et al. Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications. Am J Obstet Gynecol. 2019;220(5):480.e1-.e17.'},{id:"B48",body:'Barnhart KT. Ectopic Pregnancy. New England Journal of Medicine. 2009;361(4):379-387.'},{id:"B49",body:'Qiao C, Wang C, Zhao J, Liu C, Shang T. Elevated expression of KiSS-1 in placenta of Chinese women with early-onset preeclampsia. PLoS One. 2012;7(11):e48937.'},{id:"B50",body:'Farina A, Sekizawa A, Purwosunu Y, Rizzo N, Banzola I, Concu M, et al. Quantitative distribution of a panel of circulating mRNA in preeclampsia versus controls. Prenat Diagn. 2006;26(12):1115-1120.'},{id:"B51",body:'Abbara A, Clarke SA, Dhillo WS. Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment. Endocr Rev. 2018;39(5):593-628.'},{id:"B52",body:'Owens LA, Abbara A, Lerner A, O\'Floinn S, Christopoulos G, Khanjani S, et al. 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Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy. J Clin Endocrinol Metab. 2015;100(9):3322-3331.'},{id:"B58",body:'Franssen D, Ioannou YS, Alvarez-real A, Gerard A, Mueller JK, Heger S, et al. Pubertal timing after neonatal diethylstilbestrol exposure in female rats: Neuroendocrine vs peripheral effects and additive role of prenatal food restriction. Reproductive Toxicology. 2014;44:63-72.'},{id:"B59",body:'de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100(19):10972-10976.'},{id:"B60",body:'Navarro VM, Fernandez-Fernandez R, Castellano JM, Roa J, Mayen A, Barreiro ML, et al. Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol. 2004;561(Pt 2):379-386.'},{id:"B61",body:'Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, et al. A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med. 2008;358(7):709-715.'},{id:"B62",body:'Chan YM, Broder-Fingert S, Seminara SB. Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men. Peptides. 2009;30(1):42-48.'},{id:"B63",body:'Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab. 2005;90(5):3122-3127.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Erin Ahart",address:"eahart@kumc.edu",affiliation:'
University of Kansas Medical Center, Kansas City, KS, USA
University of Kansas Medical Center, Kansas City, KS, USA
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The causative agent, CPV‐2, was first identified in the late 1970s. CPV is a nonenveloped, linear, single‐stranded DNA virus with a genome of approximately 5 kb, and it belongs to the genus Parvovirus, together with feline panleukopenia virus, mink enteritis virus, raccoon parvovirus, and porcine parvovirus. An antigenic variant, CPV‐2a, identified within a few years after the emergence of CPV‐2, and another variant, CPV‐2b, began appearing in the canine population in 1984. In 2000, a novel antigenic variant, CPV‐2c, was first detected in Italy. This chapter focuses on the history, viral evolution, epidemiology, pathogenesis, clinical signs, diagnosis, vaccination, and prevention of CPV‐2.",book:{id:"5469",slug:"canine-medicine-recent-topics-and-advanced-research",title:"Canine Medicine",fullTitle:"Canine Medicine - Recent Topics and Advanced Research"},signatures:"Chao-Nan Lin and Shu-Yun Chiang",authors:[{id:"190874",title:"Associate Prof.",name:"Chao-Nan",middleName:null,surname:"Lin",slug:"chao-nan-lin",fullName:"Chao-Nan Lin"},{id:"194988",title:"Dr.",name:"Shu-Yun",middleName:null,surname:"Chiang",slug:"shu-yun-chiang",fullName:"Shu-Yun Chiang"}]},{id:"52705",title:"Chronic Mitral Valve Insufficiency in Dogs: Recent Advances in Diagnosis and Treatment",slug:"chronic-mitral-valve-insufficiency-in-dogs-recent-advances-in-diagnosis-and-treatment",totalDownloads:3815,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Chronic mitral valvular insufficiency (CMVI) is the most common acquired heart disease in dogs and is characterized by degenerative valvular changes causing progressive thickening of mitral leaflets and incomplete closure of mitral valve. As the disease progresses, it causes congestive heart failure (CHF) and pulmonary edema if the LA dilation cannot accommodate the volume overload by mitral regurgitation. Therefore, it is the most common cause of cardiac mortality in dogs. This chapter discusses general features of CMVI in dogs focusing on recent advances in diagnosis and treatment.",book:{id:"5469",slug:"canine-medicine-recent-topics-and-advanced-research",title:"Canine Medicine",fullTitle:"Canine Medicine - Recent Topics and Advanced Research"},signatures:"Sang-II Suh, Dong-Hyun Han, Seung-Gon Lee, Yong-Wei Hung, Ran\nChoi and Changbaig Hyun",authors:[{id:"13534",title:"Prof.",name:"Changbaig",middleName:null,surname:"Hyun",slug:"changbaig-hyun",fullName:"Changbaig Hyun"},{id:"371146",title:"Dr.",name:"Sang-II",middleName:null,surname:"Suh",slug:"sang-ii-suh",fullName:"Sang-II Suh"},{id:"371147",title:"Dr.",name:"Dong-Hyun",middleName:null,surname:"Han",slug:"dong-hyun-han",fullName:"Dong-Hyun Han"},{id:"371148",title:"Dr.",name:"Seung-Gon",middleName:null,surname:"Lee",slug:"seung-gon-lee",fullName:"Seung-Gon Lee"},{id:"371149",title:"Dr.",name:"Yong-Wei",middleName:null,surname:"Hung",slug:"yong-wei-hung",fullName:"Yong-Wei Hung"},{id:"371150",title:"Dr.",name:"Ran",middleName:null,surname:"Choi",slug:"ran-choi",fullName:"Ran Choi"}]},{id:"52484",title:"Infectious Causes of Abortion, Stillbirth and Neonatal Death in Bitches",slug:"infectious-causes-of-abortion-stillbirth-and-neonatal-death-in-bitches",totalDownloads:2793,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Problems in gestational development in dogs can be determined by infectious and non‐infectious causes. Among the non‐infectious causes, trauma during pregnancy, genetic characteristics of the animal, deficit nutrition, thyroid dysfunction, maternal problems and hormonal disorders are found. The majority of the cases are in relation to infectious diseases, one should consider viral, bacterial, fungal and protozoal, which can interfere directly or indirectly in the foetal development. The progression of foetal development may be affected by the direct action of the microorganisms to overcome the placenta, but they are also able to affect pregnancy and release placental toxins by inflammatory processes and, may still cause maternal pathologies, which entail problems such as hyperthermia, hypoxia and endotoxemia, which can result in abortion. Several diseases can trigger pregnancy loss in dogs. This action can be direct by microorganisms, as well as indirectly triggering other problems that lead to abortion. This chapter discusses the infectious aetiologies of reproductive failures (abortion, stillbirth and neonatal death) in bitches.",book:{id:"5469",slug:"canine-medicine-recent-topics-and-advanced-research",title:"Canine Medicine",fullTitle:"Canine Medicine - Recent Topics and Advanced Research"},signatures:"João Marcelo Azevedo de Paula Antunes, Débora Alves de Carvalho\nFreire, Ilanna Vanessa Pristo de Medeiros Oliveira, Gabriela Hémylin\nFerreira Moura, Larissa de Castro Demoner and Heider Irinaldo\nPereira Ferreira",authors:[{id:"191197",title:"Ph.D.",name:"João",middleName:null,surname:"Antunes",slug:"joao-antunes",fullName:"João Antunes"},{id:"191203",title:"MSc.",name:"Débora Alves",middleName:null,surname:"De Carvalho Freire",slug:"debora-alves-de-carvalho-freire",fullName:"Débora Alves De Carvalho Freire"},{id:"191204",title:"MSc.",name:"Ilanna Vanessa",middleName:null,surname:"Pristo De Medeiros Oliveira",slug:"ilanna-vanessa-pristo-de-medeiros-oliveira",fullName:"Ilanna Vanessa Pristo De Medeiros Oliveira"},{id:"191205",title:"BSc.",name:"Gabriela Hémylin",middleName:null,surname:"Ferreira Moura",slug:"gabriela-hemylin-ferreira-moura",fullName:"Gabriela Hémylin Ferreira Moura"},{id:"191207",title:"Dr.",name:"Larissa",middleName:null,surname:"De Castro Demoner",slug:"larissa-de-castro-demoner",fullName:"Larissa De Castro Demoner"},{id:"194801",title:"MSc.",name:"Heider Irinaldo Pereira",middleName:null,surname:"Ferreira",slug:"heider-irinaldo-pereira-ferreira",fullName:"Heider Irinaldo Pereira Ferreira"}]},{id:"28674",title:"Atresia Ani in Dogs and Cats",slug:"atresia-ani-in-dogs-and-cats",totalDownloads:15460,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"1667",slug:"a-bird-s-eye-view-of-veterinary-medicine",title:"A Bird's-Eye View of Veterinary Medicine",fullTitle:"A Bird's-Eye View of Veterinary Medicine"},signatures:"Lysimachos G. Papazoglou and Gary W. Ellison",authors:[{id:"85124",title:"Prof.",name:"Lysimachos",middleName:null,surname:"Papazoglou",slug:"lysimachos-papazoglou",fullName:"Lysimachos Papazoglou"},{id:"91413",title:"Prof.",name:"Gary",middleName:null,surname:"Ellison",slug:"gary-ellison",fullName:"Gary Ellison"}]}],onlineFirstChaptersFilter:{topicId:"299",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:320,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:16,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
\r\n
\r\n\t
\r\n
\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
\r\n
\r\n\t
\r\n
\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
\r\n
\r\n\t
\r\n
\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
\r\n
\r\n\t
\r\n
\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
\r\n
\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
\r\n
\r\n\t
\r\n
\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
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Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. 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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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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. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of 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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{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:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{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:"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:"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:"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:"Igor Victorovich Lakhno 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.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in 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 been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), 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 a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). 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: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",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. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",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. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:320,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. 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. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. 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. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/15636",hash:"",query:{},params:{id:"15636"},fullPath:"/profiles/15636",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()