Comparison of different organic inorganic perovskite materials with different hole and electron TLs in PSCs.
\\n\\n
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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Legumes are efficiently used as food crops for humans and animals, pulps for paper and timber manufacturing, sources for fuel and oil production, ornamental plants, and cover crops such as cereals and other staple foods. Additionally, they can be utilized for other purposes, including the production of massive amounts of organic nitrogen. This book reviews the fundamental advances related to the characterization and breeding of legume crops for improved food security. Moreover, it sheds new light on the current research trends and future research directions related to legume crop studies. This book will provoke interest for various readers, researchers, and scientists, who may find this information useful for the advancement of legume productivity.",isbn:"978-1-83968-087-8",printIsbn:"978-1-83968-086-1",pdfIsbn:"978-1-83968-088-5",doi:"10.5772/intechopen.73753",price:119,priceEur:129,priceUsd:155,slug:"legume-crops-characterization-and-breeding-for-improved-food-security",numberOfPages:122,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"4d0f73bf883bbb984cc2feef1259a9a7",bookSignature:"Mohamed Ahmed El-Esawi",publishedDate:"December 11th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7000.jpg",numberOfDownloads:7409,numberOfWosCitations:5,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:15,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:26,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 30th 2018",dateEndSecondStepPublish:"September 20th 2018",dateEndThirdStepPublish:"November 19th 2018",dateEndFourthStepPublish:"February 7th 2019",dateEndFifthStepPublish:"April 8th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"191770",title:"Dr.",name:"Mohamed A.",middleName:null,surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. El-Esawi",profilePictureURL:"https://mts.intechopen.com/storage/users/191770/images/system/191770.jpeg",biography:"Dr. Mohamed A. El-Esawi is a visiting research fellow at the University of Cambridge, United Kingdom, and Associate Professor of Molecular Genetics, Botany Department, Faculty of Science, Tanta University, Egypt. Dr. El-Esawi received his BSc and MSc from Tanta University, and his Ph.D. degree in Plant Genetics and Molecular Biology from Dublin Institute of Technology, Technological University Dublin, Ireland. After obtaining his Ph.D., Dr. El-Esawi joined the University of Warwick, United Kingdom; University of Sorbonne, France; and University of Leuven (KU Leuven), Belgium as a visiting research fellow. His research focuses on plant genetics, genomics, molecular biology, molecular physiology, developmental biology, plant-microbe interaction, and bioinformatics. He has authored several international peer-reviewed articles, book chapters, and books, and has participated in more than sixty conferences and workshops worldwide. Dr. El-Esawi is currently involved in several biological science research projects.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"9",institution:{name:"Tanta University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"350",title:"Agrology",slug:"agrology"}],chapters:[{id:"69148",title:"Introductory Chapter: Characterization and Improvement of Legume Crops",doi:"10.5772/intechopen.89369",slug:"introductory-chapter-characterization-and-improvement-of-legume-crops",totalDownloads:590,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Mohamed A. El-Esawi",downloadPdfUrl:"/chapter/pdf-download/69148",previewPdfUrl:"/chapter/pdf-preview/69148",authors:[{id:"191770",title:"Dr.",name:"Mohamed A.",surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. El-Esawi"}],corrections:null},{id:"68094",title:"Novel Therapeutic Uses of Legume Crops in Southern South America",doi:"10.5772/intechopen.85659",slug:"novel-therapeutic-uses-of-legume-crops-in-southern-south-america",totalDownloads:1120,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The Argentine flora comprises more than 10,000 species, and many of them have been recorded as having medicinal, antimicrobial, and nutraceutical uses in humans as well as veterinary uses. In this chapter, native species/populations from the north of Argentina have been identified, selected, and characterized using morphological, chemical, and molecular techniques. Bauhinia forficata subsp. pruinosa was found to have anti-inflammatory, antidiabetic, diuretic, and analgesic activity and Senna spectabilis var. spectabilis has been found to have antibacterial, antibiofilm, antifungal, and antioxidant properties. The characterization and conservation of the native germplasm will allow us to propose future protocols of adaptation and technological processes to improve the quality of life in the rural areas and sustainable growth. This process will be achieved through a future integral and rational use that contemplates the conservation of the wild populations and their habitat. Thus, new resources will be generated, and the native flora of the country will gain value, strengthening the regional and territorial development of the agricultural and agroindustrial system. In addition, the domestication practices oriented to an integral management of the crop without extraction of the biological resource from the natural habitat minimize the impact of ecosystem degradation by overexploitation associated with landscape fragmentation.",signatures:"Renée Hersilia Fortunato, Virginia Fuentes Baluzzi, Fernando De Diego, Rodrigo T. Biagioni and Alejandro Daniel Esquivel",downloadPdfUrl:"/chapter/pdf-download/68094",previewPdfUrl:"/chapter/pdf-preview/68094",authors:[{id:"272187",title:"Dr.",name:"Renée",surname:"Fortunato",slug:"renee-fortunato",fullName:"Renée Fortunato"},{id:"288386",title:"BSc.",name:"Virginia",surname:"Fuentes Baluzzi",slug:"virginia-fuentes-baluzzi",fullName:"Virginia Fuentes Baluzzi"},{id:"288387",title:"MSc.",name:"Fernando",surname:"De Diego",slug:"fernando-de-diego",fullName:"Fernando De Diego"},{id:"288388",title:"Mr.",name:"Rodrigo",surname:"Biagioni",slug:"rodrigo-biagioni",fullName:"Rodrigo Biagioni"},{id:"288390",title:"Mr.",name:"Alejandro",surname:"Esquivel",slug:"alejandro-esquivel",fullName:"Alejandro Esquivel"}],corrections:null},{id:"64900",title:"Ethnomedicinal Values of Legume Plants in Pakistan",doi:"10.5772/intechopen.82762",slug:"ethnomedicinal-values-of-legume-plants-in-pakistan",totalDownloads:673,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The data on medicinal plants in the vegetation of Pakistan was studied and surveyed from September to November, 2018. Different ethnomedicinal species were recorded which are used by local inhabitants as a medicine, fodder, fuel, and for agricultural purpose. Many of the medicinal plants recorded are used for the treatment of two or more diseases by the local people. The family Fabaceae was dominant with respect to medicinal plants. The precious knowledge of medicinal flora is rapidly vanishing due to the illiteracy among the local people and also due to destruction of the medicinal plants. The present study was designed to convey the knowledge and importance of medicinal flora as well as traditional uses of such plants in daily life.",signatures:"Faisal Hussain and Farzana Usman",downloadPdfUrl:"/chapter/pdf-download/64900",previewPdfUrl:"/chapter/pdf-preview/64900",authors:[{id:"199137",title:"Dr.",name:"Faisal",surname:"Hussain",slug:"faisal-hussain",fullName:"Faisal Hussain"},{id:"272448",title:"Dr.",name:"Farzana",surname:"Usman",slug:"farzana-usman",fullName:"Farzana Usman"}],corrections:null},{id:"66497",title:"Starch Granules from Cowpea, Black, and Carioca Beans in Raw and Cooked Forms",doi:"10.5772/intechopen.85656",slug:"starch-granules-from-cowpea-black-and-carioca-beans-in-raw-and-cooked-forms",totalDownloads:1092,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Starch applications in food systems are mainly influenced by solubility, gelatinization, paste viscosity, digestibility, and retrogradation. These characteristics result from properties such as the size and shape of granules, amylose and amylopectin contents, distribution of polymer chains, degree of crystallinity, and extraction of waste. In beans, the percentage of starch contents on dry basis is between 45 and 60%, being 24–65% amylose. This chapter evaluated the structure of common beans starch granules (Phaseolus vulgaris) and cowpea (Vigna unguiculata) in raw and cooked forms, by optical microscopy (OM) and scanning electron microscopy (SEM). Thus it was possible to observe the gelatinization of the starch granules especially in cowpea and carioca beans, as well as the “hard-to-cook” phenomenon in the black beans.",signatures:"Joyce Aparecida Tavares de Miranda, Lucia Maria Jaeger de Carvalho, Izabela Miranda de Castro, José Luiz Viana de Carvalho, André Luiz de Alcântara Guimarães and Ana Cláudia de Macêdo Vieira",downloadPdfUrl:"/chapter/pdf-download/66497",previewPdfUrl:"/chapter/pdf-preview/66497",authors:[{id:"97047",title:"Prof.",name:"Lucia Maria Jaeger",surname:"De Carvalho",slug:"lucia-maria-jaeger-de-carvalho",fullName:"Lucia Maria Jaeger De Carvalho"},{id:"200652",title:"Dr.",name:"André",surname:"Guimarães",slug:"andre-guimaraes",fullName:"André Guimarães"},{id:"209351",title:"Dr.",name:"Joyce",surname:"Miranda",slug:"joyce-miranda",fullName:"Joyce Miranda"},{id:"209473",title:"Dr.",name:"Izabela Miranda De",surname:"Castro",slug:"izabela-miranda-de-castro",fullName:"Izabela Miranda De Castro"},{id:"276507",title:"Dr.",name:"Ana",surname:"Vieira",slug:"ana-vieira",fullName:"Ana Vieira"},{id:"295486",title:"MSc.",name:"Jose",surname:"Carvalho",slug:"jose-carvalho",fullName:"Jose Carvalho"}],corrections:null},{id:"66478",title:"Mungbean (Vigna radiata L. Wilczek): Retrospect and Prospects",doi:"10.5772/intechopen.85657",slug:"mungbean-em-vigna-radiata-em-l-wilczek-retrospect-and-prospects",totalDownloads:1239,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Mungbean (Vigna radiata L. Wilczek) is economically most important crop of Vigna group. It is also known as green gram, golden gram, moong, Chickasaw, Oregon pea, and chop suey bean and this legumes have a strategic position in Southeast Asian countries for nutritional security and sustainable crop production. Being rich in quality protein, minerals and vitamins, they are inseparable ingredients in the diets of a vast majority of Indian population. When supplemented with cereals, they provide a perfect mix of essential amino acids with high biological value. These crops have the ability to fix atmospheric nitrogen (58–109 kg per ha in kg per ha mungbean) in symbiotic association with Rhizobium bacteria, which enables them to meet their own nitrogen requirement and also benefit the succeeding crops. This crop has also been reported to smother weed flora appreciably (20–45%) when intercropped with tall cereals or pigeonpea and consequently, minimize the cost incurred on weed control. On account of short duration and photo-thermo insensitivity, they are considered excellent crops for crop intensification and diversification. A seed of mungbean is highly nutritious containing 24–28% protein, 1.0–1.5% fat, 3.5–4.5% fibre, 4.5–5.5% ash and 59–65% carbohydrates on dry weight basis and provide 334–344 kcal energy. Mungbean protein is considered to be easily digestible. Mungbean are tropical grain legumes widely grown in the sub-tropical countries of South and Southeast Asia. Nevertheless, these crops are cultivated over a wide range of latitudes in the regions where average diurnal temperatures during the growing season are warmer than about 20°C.",signatures:"Suhel Mehandi, Syed Mohd. Quatadah, Sudhakar Prasad Mishra, Indra Prakash Singh, Nagmi Praveen and Namrata Dwivedi",downloadPdfUrl:"/chapter/pdf-download/66478",previewPdfUrl:"/chapter/pdf-preview/66478",authors:[{id:"275243",title:"Dr.",name:"Suhel",surname:"Mehandi",slug:"suhel-mehandi",fullName:"Suhel Mehandi"},{id:"275245",title:"Dr.",name:"Indra Prakash",surname:"Singh",slug:"indra-prakash-singh",fullName:"Indra Prakash Singh"},{id:"275246",title:"Prof.",name:"Sudhakar",surname:"Prasad Mishra",slug:"sudhakar-prasad-mishra",fullName:"Sudhakar Prasad Mishra"},{id:"290295",title:"Dr.",name:"Syed",surname:"Mohd. Quatadah",slug:"syed-mohd.-quatadah",fullName:"Syed Mohd. Quatadah"},{id:"290728",title:"MSc.",name:"Nagmi",surname:"Praveen",slug:"nagmi-praveen",fullName:"Nagmi Praveen"},{id:"290731",title:"Dr.",name:"Namrata",surname:"Dwivedi",slug:"namrata-dwivedi",fullName:"Namrata Dwivedi"}],corrections:null},{id:"64941",title:"The Productivity of Selected Species and Cultivars of Legumes Grown for Seeds in Organic Production System",doi:"10.5772/intechopen.82686",slug:"the-productivity-of-selected-species-and-cultivars-of-legumes-grown-for-seeds-in-organic-production-",totalDownloads:540,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The aim of the study was to assess the yielding of selected legume species with diversified morphological structure cultivated for seeds in ecological system. The field experiment was carried out in 2016–2018. The first factor was legume species: faba bean, field pea, yellow lupine, and blue lupine, and the second factor was varieties of legumes: faba bean (Granit and Amulet), field pea (Hubal and Batuta), blue lupine (Kurant and Regent), and yellow lupine (Bursztyn and Perkoz). After the harvest, the grain yield of legume plants and the weight of a thousand seeds were determined. The plant structure was determined (length of the part of fruiting stem, number of pods and seeds per plant, number of seeds in the pod, number of fruiting nodes, number of pods and seeds from the node). In addition, the content of selected nutrients (protein, fiber, fat, macroelements) was determined in seeds. Studies showed that in ecological conditions, the pea cultivation, especially Hubal variety (with bipinnate leaves), enabled obtaining the largest seed yield, while the smallest seed yields yellow lupine independent of the morphological type. The self-completing varieties of faba bean, yellow lupine, and blue lupines were yielded at a higher level than varieties with a traditional growth type. Among the pea varieties assessed, the variety Hubal yielded better (with bipinnate leaves). Significantly, higher yield of protein is provided by faba bean cultivation, while the smaller level of pea and yellow lupine.",signatures:"Księżak Jerzy and Bojarszczuk Jolanta",downloadPdfUrl:"/chapter/pdf-download/64941",previewPdfUrl:"/chapter/pdf-preview/64941",authors:[{id:"170281",title:"Prof.",name:"Jerzy",surname:"Księżak",slug:"jerzy-ksiezak",fullName:"Jerzy Księżak"},{id:"170282",title:"Dr.",name:"Jolanta",surname:"Bojarszczuk",slug:"jolanta-bojarszczuk",fullName:"Jolanta Bojarszczuk"}],corrections:null},{id:"64927",title:"Influence of Adjuvants on Efficacy of Postemergence Herbicides Commonly Used in Peanut (Arachis hypogaea L.)",doi:"10.5772/intechopen.82708",slug:"influence-of-adjuvants-on-efficacy-of-postemergence-herbicides-commonly-used-in-peanut-em-arachis-hy",totalDownloads:903,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Field studies were conducted for 2 years in the High Plains of Texas (34.1826o N, 101.9505o W) and in South Texas (29.1634o N, 97.0725o W) to evaluate weed control when using different adjuvants with commonly used peanut herbicides. In the High Plains, Amaranthus palmeri L. control with acifluorfen, imazapic, lactofen, and 2,4-DB at the 1X dose improved with the use of an adjuvant over no adjuvant. A. palmeri control with imazethapyr was similar to that seen with imazapic and lactofen with the exception of the 1/2X rate of imazethapyr, which showed improved control with Agridex over the use of no adjuvant or Induce in 1 year, while Induce was better than no adjuvant or Agridex in the other year. In 1 year in South Texas, A. palmeri control with imazapic at the 1X dose was ≥73% with/without an adjuvant. In another year, the 1X dose of imazapic controlled A. palmeri 64% without an adjuvant, while the addition of Cide Kick II resulted in 83% control. An adjuvant did not improve A. palmeri control with lactofen or Cucumis melo L. control with either imazapic or lactofen. Urochloa texana (Buckl.) control with clethodim at the 1X dose was not improved by the addition of an adjuvant in either year. U. texana control was not improved when using the 1X dose of fluazifop-P with any adjuvant.",signatures:"William James Grichar, Peter A. Dotray and Mark A. Matocha",downloadPdfUrl:"/chapter/pdf-download/64927",previewPdfUrl:"/chapter/pdf-preview/64927",authors:[{id:"13502",title:"Prof.",name:"W. James",surname:"Grichar",slug:"w.-james-grichar",fullName:"W. James Grichar"},{id:"14656",title:"Dr.",name:"Peter A.",surname:"Dotray",slug:"peter-a.-dotray",fullName:"Peter A. Dotray"},{id:"283163",title:"Prof.",name:"Mark",surname:"Matocha",slug:"mark-matocha",fullName:"Mark Matocha"}],corrections:null},{id:"65957",title:"Breeding Elite Cowpea [Vigna unguiculata (L.) Walp] Varieties for Improved Food Security and Income in Africa: Opportunities and Challenges",doi:"10.5772/intechopen.84985",slug:"breeding-elite-cowpea-em-vigna-unguiculata-em-l-walp-varieties-for-improved-food-security-and-income",totalDownloads:1255,totalCrossrefCites:3,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Cowpea, Vigna unguiculata (L.) Walp, is among the most important grain legumes in Africa. Its nutritional value and biological nitrogen fixation (BNF) potential coupled with a high plasticity to environmental conditions places this legume in a unique position in Sub-Saharan Africa (SSA) in the context of food and nutritional security. However, cowpea yield and BNF contribution to agricultural systems in this sub-continent is far behind the average global values. The inability to run effective breeding programs to timely generate and deliver high yielding, nutritious and climate smart cowpea varieties, coupled with poor crop husbandry practices has been in the forefront of the current situation. In this chapter, the main constrains and opportunities to establish and run successful and effective cowpea production and breading programs in SSA are discussed. The discussion is built around the argument that SSA can benefit from its rich collection of landraces, as well as from high-throughput methodologies to assist the screening and the development of adapted, high yielding and nutritious varieties.",signatures:"Ana Maria Figueira Gomes, Nascimento Nhantumbo, Manuela Ferreira-Pinto, Rafael Massinga, José C. Ramalho and Ana Ribeiro-Barros",downloadPdfUrl:"/chapter/pdf-download/65957",previewPdfUrl:"/chapter/pdf-preview/65957",authors:[{id:"171036",title:"Dr.",name:"Ana I.",surname:"Ribeiro-Barros",slug:"ana-i.-ribeiro-barros",fullName:"Ana I. Ribeiro-Barros"},{id:"275914",title:"MSc.",name:"Ana",surname:"Gomes",slug:"ana-gomes",fullName:"Ana Gomes"},{id:"275915",title:"Prof.",name:"Nascimento",surname:"Nhantumbo",slug:"nascimento-nhantumbo",fullName:"Nascimento Nhantumbo"},{id:"275916",title:"Prof.",name:"Rafael",surname:"Massinga",slug:"rafael-massinga",fullName:"Rafael Massinga"},{id:"275917",title:"Dr.",name:"José",surname:"Ramalho",slug:"jose-ramalho",fullName:"José Ramalho"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5781",title:"Phytohormones",subtitle:"Signaling Mechanisms and Crosstalk in Plant Development and Stress Responses",isOpenForSubmission:!1,hash:"054eaa85c13ebe3d04fb8852005d2bad",slug:"phytohormones-signaling-mechanisms-and-crosstalk-in-plant-development-and-stress-responses",bookSignature:"Mohamed El-Esawi",coverURL:"https://cdn.intechopen.com/books/images_new/5781.jpg",editedByType:"Edited by",editors:[{id:"191770",title:"Dr.",name:"Mohamed A.",surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. 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Organic-inorganic perovskites materials have emerged as a promising material for high-efficiency nanostructured devices such as light-emitting diodes (LEDs), detectors, field-effect transistors, and photovoltaic devices etc. [1, 2]. Organic-inorganic perovskites have attracted extensive attention due to their promising optical and electronic properties, excellent crystallinity, adjustable bandgap, long charge diffusion length, electroluminescence, and conductivity [3, 4]. As the most fascinating new-generation photovoltaic materials, organic–inorganic perovskite due to their facile synthesis, low temperature deposition, and capability to make flexible devices has been considered as a vigorous component of the efficient, low-cost, lightweight and flexible Perovskite solar cells [3, 4]. Perovskite solar cells (PSCs) have rapidly become the leading edge of third generation 3G photovoltaic technologies [5, 6]. PSCs based on the organic inorganic perovskite materials have fascinated great consideration, with their power conversion efficiencies (PCEs) reaching 25.2% certified [7, 8]. Over the past several months, it has been observed a surprising revolution and rapid progress in the field of emerging photovoltaic, with the understanding of highly efficient solar cells based on organic inorganic perovskite materials. This perovskite technology is now well-matched with the 1G and 2G technologies and is thus probably be embraced by the conventional photovoltaic community and industry [9, 10].
The advent of organic inorganic perovskite based solar cells has resulted in rapid growth in photovoltaic history. Organic inorganic perovskite materials have recently, fascinated greater attention due to its outstanding light-harvesting features [7].
Organic-inorganic perovskite absorbers have appeared in the field of DSSCs since 2009. The first perovskite-sensitized DSSCs were developed by Kojima et al. [11] which obtained PCE of 3.13% using liquid electrolytes. However, continuous irradiation produced a photocurrent decay in an open cell when exposed to air. Later, the electron transporting layer (Titania) surface and perovskite processing were optimized, and in 2011, Im et al. [12] developed first stable PSC, using CH3NH3PbI3-based iodide liquid electrolyte offered a PCE of 6.5%. However, the perovskite nanocrystals dissolved in the liquid iodide electrolyte solution, and the cell degraded within 10 minutes. To avoid the problem of perovskite dissolution in an electrolytic solution, the liquid electrolyte was replaced by a solid in 2012, and a PCE of 9% was achieved showing good stability up to 500 h without significant losses [13, 14]. Afterward, Al2O3 an insulating network was used to substitute conducting nano porous TiO2. By using mixed MAPbI3-XClX as the sensitizer, an enhanced open-circuit voltage (VOC) and PCE (10.9%) was achieved [15]. In 2013, a successive deposition method for the perovskite layer within the porous metal oxide film was developed. The fabrication technique for solid-state mesoscopic solar cells greatly improved the reproducibility of cell performance and produced a high PCE of 15%. Many PSC devices are now attaining PCE > 20% since 2015 and 25% in 2019 [4, 16]. National Renewable Energy Laboratory (NREL), on 3rd August 2019 declared a new world record PCE of 25.2% for PSCs. This PCE value is improved up to ∼28% for perovskite-silicon tandem structures [4].
PSC consists of a perovskite absorbing material sandwiched between electron transporting layer (ETL) and hole-transporting layer (HTL) along with the transparent conducting oxide substrate (FTO) and a top electrode such as gold, silver [17]. In PSCs, the effective charge separation and the light harvesting efficiency are significantly affected by the properties like particle size, porosity, surface area, surface morphology, band gap, thickness of semiconductor materials, and the nature of organometal halide perovskites [18].
The primary function of an
The HTL lies in the heart i.e. in between the metal electrode and perovskite of device. It plays a central-role in the PSC and extracts holes from the perovskite and transfer them to top-electrode. It avoids the direct contact of perovskite and top electrode [22]. For efficient hole transport, the highest occupied molecular orbit (HOMO) must match the valence band (VB) of perovskite materials. According to the chemical composition, HTMs in PSCs can be divided into two types: organic and inorganic HTMs. Spiro-OMeTAD is the most used organic HTM, which displays good penetration in perovskite and is an appropriate match with the VB energy of perovskite, though its hole mobility is not as superior as that of other organic HTMs. [21, 23]. Hence, in order to improve the hole mobility, polymers are doped with
A PSC includes an organic-inorganic perovskite material as the light-harvesting active layer. Amongst the component’s PSCs, perovskite materials perform a key role. Perovskite is comprised of earth abundant and inexpensive materials. It is processed at lower temperature rather via the printing techniques [26]. The organic−inorganic perovskites can exhibit appropriately good ambipolar charge transport and the primary functions of photovoltaic operation comprising light absorption, generation of charges, and transport of both electrons and holes. They perform both as efficient light absorbers and charge carriers [21]. The commonly used perovskites are Methylammonium lead triiodide (CH3NH3PbI3) and formamidinium lead triiodide (CH3(NH2)2PbI3) [27]. Moreover, The PSC architecture is represented in Figure 1.
Representative architecture of PSC.
The two main device architectures of PSC are
mesoscopic
planar
The conventional PSC consists of mesoscopic n-i-p structure and is the novel architecture of PSC devices which consists of an FTO, an electron transport layer (ETL), a mesoporous oxide layer such as TiO2, or SnO2, perovskite (light absorbing) layer, a hole transport layer (HTL), and an electrode layer. The mesoporous TiO2 layer played a significant role in the electron transfer process and as a scaffold providing mechanical support of the perovskite crystal. The use of mesoporous materials in PSC permit the perovskite material to adhere to the mesoporous metal oxide framework to increase the light-receiving area of the photosensitive material and results in improving the efficiency of the device. The mesoporous layer was usually less than 300 nm. The presently mesoporous structure of PSCs is one of the most common structures with a power conversion efficiency (PCE) greater than 20% [28]. The mesoscopic structure due to the fabrication ease and outstanding best efficiencies is the most extensively adopted in research labs. However, high temperature (˃450°C) sintering is required for mesoporous layer-based devices, which prevents the use of plastic substrates [29, 30, 31]. To overcome this problem, the planar perovskite solar cell was developed that showed comparable performance for mesoporous perovskite solar cell. Planar heterojunction PSCs have been reported by several researchers in which only compact layers of ETM and HTM is used without a mesoporous layer at a temperature lower than 200°C [19, 21, 32]. Hence the planar structure turns out to be very attractive for basic research purposes. The mesoscopic and planar structures of PSC are represented in Figure 2.
Representative scheme of a mesoporous (right) and planar PSC (left).
Perovskites materials are designated by the formula ABX3, where A and B are cations of different sizes (A being larger than B) and X is an anion [7]. The crystal structure of perovskites is depicted in Figure 3 and it has a cubic crystal structure with three-dimensional (3D) framework sharing BX6 octahedron with the A ion placed at the octahedral interstices [33, 34]. In organic-inorganic materials, the A is organic cations generally methylammonium, ethylammonium and formamidinium and B is usually metal ions of group IV such as Pb2+, Sn2+ and Ge2+ whereas the X are VII group anions I−, Cl− and Br− [2, 7, 34].
Structure of perovskite.
The crystallographic stability and probable structure of perovskite can be inferred by studying a “tolerance factor” t and an “octahedral factor” μ. A “tolerance factor” is defined as the “ratio of the A-X distance to the B-X distance in an idealized solid-sphere model” and is represented by the formula:
where RA, RB and RX are the ionic radii of the corresponding ions.
An “octahedral factor” is defined as “the ratio
For halide (X = F, Cl, Br, I) perovskites, generally 0.81 < t < 1.11 and 0.44 < μ < 0.90 [35]. If t value lies in the narrow range 0.89–1.0, the structure is cubic, but, if it is lower, symmetric tetragonal or orthorhombic structures is expected [2]. Regardless of these limitations, conversions between these structures are common on heating, at the high-temperature cubic phase is generally obtained.
For the organic–inorganic perovskites, organic cation A usually methylammonium (CH3NH3+) with RA = 0.18 nm, ethylammonium (CH3CH2NH3+) (RA = 0.23 nm) and formamidinium (NH2CHNH2+) (RA = 0.19–0.22 nm) are used. The cation B is commonly Pb (RB = 0.119 nm); however, Sn (RB = 0.110 nm) forms similar compounds with more ideal bandgap but exhibits lower stability (ascribed to the oxidation of Sn to SnI4 in the iodide perovskite). The anion X is a halogen, generally iodine (RX = 0.220 nm) is used, however Br and Cl are also used (RX = 0.196 nm and 0.181 nm) [35, 36]. The commonly used organic inorganic perovskite material is methylammonium lead triiodide (CH3NH3PbI3).
MAPbX3 perovskite show multiple phases as a function of composition and temperature. These different phases have markedly different optical and electrical properties as well as stability. MAPbI3 displayed α-phase, δ-phase, and γ-phases with transition temperatures of 400 K, 333 K, and 180 K, respectively. Generally, the δ-phase MAPbI3 is used as absorber in solar cell due to its thermodynamically stable nature at room temperature and its increased conductivity and absorption coefficient (>26 mm_1) in contrast to the α-phase. Though, a phase transition from δ-phase to α-phase may occur under continuous 1 sun illumination [15].
The deposition technique of organic-inorganic perovskites films is quite an important issue for perovskite studies, because the possible use of perovskite materials depends on the availability of simple and perfect thin film deposition method. As concerns the preparation methods of organometallic halide perovskite CH3NH3PbX3 thin films, solution-based procedures have been proposed to manufacture thin films. However, deposition of organic-inorganic perovskite materials is often challenging due to different physical and chemical properties of the organic and inorganic parts of perovskite materials [15]. Despite of this, several significant methods are used for thin film deposition of organic-inorganic hybrid perovskites. Various methods used for perovskite deposition are solution-processed (one-step and two-step) deposition, evaporation method, and vapor assisted solution process (VASP) are the typically adopted methods for film deposition [15, 37, 38].
one-step precursor solution deposition (Spin-coating technique)
two-step sequential deposition (including the vapor-assisted solution process)
thermal evaporation technique
One-step processing (spin-coating) is a suitable technique extensively applied for uniform thin film deposition and is based on the co-deposition of both the inorganic and organic components either through solution processing or thermal evaporation. In solution processing, a mixture of both MX2 (M ¼ Pb, Sn; X ¼ Cl-, Br-, I-) and AX (A ¼ methylammonium MA); formamidinium, FA) is dissolved in an organic solvent and deposited through the spin coating to form a film (Figure 4), followed by annealing to produce the perovskite layer [15]. The post deposition annealing of the films at low temperature (T < 250°C) is sometimes used to increase phase purity and crystallinity [6]. Spin-coating allows deposition of hybrid perovskites on various substrates, containing glass, quartz, plastic, and silicon. Selection of suitable parameters such as substrate, spin speed and the substrate temperature are essential for this technique and can be selected accordingly. The wetting properties of the solution on the chosen substrate can be improved by pre-treating the substrate with a suitable adhesion agent. The spin-coating technique does not involve cumbersome equipment and it gives high-quality films in quite short time at room temperature. It is considered as a distinct case of solution crystal growth, which results in the formation of highly oriented perovskites layer on a substrate. In order to obtain a layer with the desired thickness, optimization of various parameters such as concentration of perovskites solution, and spin-coating parameters (spin speed, acceleration and spin duration) can be carried out. Generally, 2D homogeneous perovskites films with a thickness ranging 10 nm to 100 nm can be obtained by carefully choosing the parameters. The selection of solvent is also important by considering the solubility for both the organic ammonium and the inorganic lead halide. The usually used solvents for spin coating technique are Dimethylformamide (DMF) or Dimethyl sulfoxide (DMSO) [39]. These spin-coated perovskites films are very reproducible, and this technique is suitable for all PSC structures (mesoporous vs. planar) [39].
Schematic of the spin-coating process [
Mitzi [40] first time reported the two-step dipping technique in 1998, and later by Burschka et al. [41] in 2013. In a two-step dip-coating deposition process, a metal halide PbI2 layer is first deposited by vacuum evaporation or spin-coated on a substrate. Then this coated film is altered into the perovskite by dipping into an organic MAI solution as it is shown in Figure 4. This method offered PCE of 15% and certified 14.14% [39]. Suitable selection of solvent is important for the dipping process. The solvent is selected such that can dissolve organic salt but cannot metal halide and the final organic-inorganic perovskite, toluene/2-propanol mixture is an appropriate solvent for the organic salt. The organic cations in solution intercalate into and react with metal halide on the substrate and form a crystalline film [6]. The dipping times are quite short: several seconds to minutes, depending on the system. This method is a suitable method for a variety of inorganic and organics, even if they have an incompatibility in solubility. This process effectively reduces the chemical reaction between the perovskite and the underlying ETL. The development of successive deposition methods has offered a variety of ETL options, though allowing for perovskite films to be prepared successfully at room temperature [15]. In addition, Chen et al. [42] developed a vapor assisted solution processing (VASP) method that used the reaction between MAI vapor and pre-deposited PbI2 to form the completed perovskite film. The resulting MAPbI3 exhibits excellent film quality.
M. Era et al. [43] first used thermal evaporation method. They used the dual source vapor deposition by using ammonium iodide RNH3I and lead iodide PbI2, organic and inorganic source were co-evaporated and deposited on quartz. The pressure of evaporation chamber was about 10−6 Torr. By using this method, it is possible to precisely control the smoothness and thickness of the films. However, it is often hard to balance the organic and inorganic rates, which is important in attaining the correct composition of the resultant perovskite films. Furthermore, Mitzi et al. [40] developed another method, by using a single evaporation source to deposit perovskites thin films called single source thermal ablation (SSTA) technique. This consists of a vacuum chamber, with an electrical feed-through to a thin tantalum sheet heater. A suspension of insoluble powders in a drying solvent is placed on the heater. Under a suitable vacuum, the temperature goes to approximately 1000°C in 1–2 second, the whole starting charge ablates from the heater. After ablation, the organic and inorganic parts reassemble on the substrates to yield films of the chosen product. Liu et al. [44] in 2013, improved this technique as a dual-source vapor deposition method for pinhole-free MAPbI1−xClx perovskite films with a thickness of hundreds of nanometers for planar PSCs.
Later on, the chemical vapor deposition (CVD) method was reported by Leyden et al. [45], which precisely control the crystallization process. Vapor deposition methods are appropriate for multi-layered thin-film and a variety of substrates, though needs high vacuum [39]. However, this method has drawbacks of yield and therefore is not very effectively employed at industrial scale [46]. Though great achievements have been attained, researchers still meet some challenges, involving reproducibility and grain boundaries of perovskite films which are considered as a defect region initiates carrier recombination and accelerates device degradation. Hence, efforts to increasing grain size and reducing grain boundary of films are critical for stable and highly efficient PSCs.
The possibility of merging the properties of inorganic with those of organic solids has inspired intensive research into the versatile properties. Organic-inorganic perovskite materials have been widely used in PSCs using different ETLs and HTLs. The optimization of materials and structures is one of the solutions to improve the PCE. Table 1 shows some representative devices and their architectures and performance.
ETL | HTL | Perovskite | PCE | References |
---|---|---|---|---|
Gr/ZnO-QDs | Spiro-OMeTAD | CH3NH3PbI3 | 9.73 | [18] |
TiO2-Al2O3 | Spiro-OMeTAD -Li-TFSI | — | 10 | [24] |
ZnO-NPs | Spiro-OMeTAD | CH3NH3PbI3 | 10.2 | [34] |
TiO2 | Spiro-OMeTAD | CH3NH3PbI3-xClx | 11.7 | [47] |
TiO2 | Spiro-OMeTAD | CH3NH3PbI3 | 15.4 | [48] |
TiO2 | — | CH3NH3Pb Br3−n | 8.54 | [49] |
SnO2 QD | Spiro-OMeTAD-Li-TFSI | Cs0.05(MA0.17FA0.83)0.95Pb(I0.83Br0.17)3 | 20.79 | [50] |
SnO2 QD | Spiro-OMeTAD-Li-TFSI | CH3NH3PbI3 | 19.73 | [50] |
SnO2 | Spiro-OMeTAD | Cs/MA/FA perovskite | 20.7 | [51] |
SnO2 QD | Spiro-OMeTAD | CH3NH3PbI3 | 19.12 | [52] |
TiO2 | Spiro-OMeTAD | (FAI)0.81(PbI2)0.85(MAPbBr3)0.15 | 21.02 | [53, 54] |
Comparison of different organic inorganic perovskite materials with different hole and electron TLs in PSCs.
Methylammonium Lead halide perovskites (MAPbX3) are mostly regarded as promising light absorbers owing their many advantages comprising high absorption coefficients, optimal bandgaps, and long-range exciton diffusion lengths. These perovskites have led to solar cells with PCEs upto15% in combination with meso-structure metal oxides and deposition methods (such as sequential and vapor deposition) [34]. There were few attempts to synthesize new perovskites by changing halide anions (X) in the MAPbX3 structure, but these materials did not result too much improvement in device efficiency. Optical and electronic properties of organo lead halide perovskites have been considered by replacing MA cation with other organic cations such as ethyl ammonium and formamidinium [55].
Dkhissi et al. [32] fabricated an efficiently CH3NH3PbI3-based planar perovskite solar cells on polymer substrates at 150°C or below. The hole blocking layer employed is a TiO2 layer. The devices showed an average efficiency of 10.6 ± 1.2%, and a maximum efficiency of 12.3% for flexible perovskite solar cells, presenting great potential for further enhancement of the low-cost, low-temperature processing solar technology.
In 2014, Choi et al. [55] modified perovskite material with Cesium (Cs) by doping methyl ammonium lead iodide perovskites by Cesium to improve the performance of inverted-type perovskite/fullerene planar heterojunction hybrid solar cells. CsxMA1-xPbI3 perovskite devices achieved improvement in device efficiency from 5.51–6.8% with an optimized 10% Cs doping concentration. The devices exhibited an outstanding increase in efficiency due to increases in short-circuit current density and open-circuit voltage.
CH3NH3PbBr3 and CH3NH3PbI3, were used as sensitizers for TiO2 in a liquid junction solar cell, with open-circuit voltages of 0.61 and 0.71 V were achieved. CH3NH3PbI3 on mesoporous TiO2 showed good charge transport properties, where the perovskite is both the absorber and the hole conductor. Further CH3NH3PbX3 (X = Br, I), mixed perovskite lead halides i.e., CH3NH3PbI2Cl, CH3NH3PbBr3 − xClx, and CH3NH3PbI3 − xClx were studied [27].
Giacomo et al. [47] fabricated PSCs using CH3NH3PbI3-xClx with different hole-transporting materials. The mostly used Spiro-OMeTAD has been compared to the P3HT. By changing the energy level of P3HT and optimizing the device fabrication, PCE reached to 9.3%. They showed that P3HT can be used a suitable low-cost hole transport material for efficient perovskite based solar cells.
NiO has been tried as a substitute for organic molecular or polymeric HTMs (spiro-MeOTAD), displaying encouraging results in the TiO2/CH3NH3PbI3 configuration, a PCE of 9.5% was attained with nanocrystalline NiO layer. As the valence band edge (5.4 eV) for NiO is near to that of iodide perovskite (5.3 eV), so post-treatment of NiO film by means of UV light or oxygen plasma is vital to progress hole injection efficiency due to an increase in the work function of NiO by such post treatments. UV-ozone post-treated NiO usually has a greater photovoltaic performance than untreated NiO, due to change in work function and an enhancement in wettability indicating a better chemical interaction between perovskite and NiO [36].
The use of perovskites with mixed cations and halides has become significant for PV applications which are mainly MAPbX3, FAPbX3 and CsPbX3 (X = Br or I). on the introduction of MA into FA brings the crystallization of FA perovskite (because MA is slightly smaller than FA) which allows a large fraction of the yellow phase to continue. MA/FA compounds show notable PCEs and therefore the development of these compounds is an opportunity in the advancement of PSCs. Saliba et al. [56] introduces an innovative approach using a triple Cs/MA/FA cation mixture where Cs is used to progress MA/FA perovskite compounds. A small amount of Cs is enough to efficiently suppress yellow phase impurities allowing the preparation of pure, defect-free perovskite films.
Song et al. [57] reported that the combination of FA decreases the release of organic species but does not stop the formation of I/HI. Though, the addition of Cs successfully overcomes the release of all volatile gases. The best photostability is found with FA/Cs mixed perovskites, presenting the complete removal of MA from mixed-cation perovskite is favored for more photostable perovskites.
As CH3NH3PbI3 has ambipolar properties and is slightly more p-type than n-type and is satisfactory to develop p-n junction-like devices without an HTM, known as HTM-free photovoltaic cells. CH3NH3PbI3 could act both as light absorber and hole transporter in a CH3NH3PbI3/mesoporous TiO2 heterojunction device with a PCE of 5.5%. It was observed that HTM-free perovskite solar cells had a poor FF and a low Voc as compared to those with an HTM, which is related to the larger shunt current along with a lower IPCE for these devices [2].
Different proportions of inorganic (Pb, Sn) cations, organic cations and halide anions (I, Br, Cl) can be combined in mixed perovskites, permitting their properties to be fine-tuned [35]. Tuning of bandgap of MAPbX3 has been attained through the substitution of I with Cl/Br ions, which occurs from a dependence of electronic energies on the effective exciton mass. The optical absorption can be tuned by bandgap engineering to comprise the whole visible spectrum. In the meantime, the combination of Cl/Br into iodide-based structure has markedly advanced the charge transport and the separation kinetics within the perovskite layer. Hence, by tuning the composition of perovskite resulted in improved efficiency and the stability of PSCs. It was observed that an increase in the size of perovskite cation materials resulted in a reduction in the bandgap. A tunable bandgap can be obtained (between 1.48 and 2.23 eV) by replacing the methylammonium with a slightly larger formamidinium cation. Significantly, the reduced bandgap led to a PCE of up to 14.2% and high short circuit currents (>23 mA cm−2) [31].
CH3NH3SnI3 is demanded to be a low-carrier-density p-type metal. Theoretical calculations on perovskite recommended that their electronic properties intensely depend on the structure of the inorganic cage and formation of the perovskite octahedral network. By changing the inorganic and organic components and their stoichiometric ratio, it is probable to control the system dimensionality and electronic and optical properties. Furthermore, the presence of weak bonds in the perovskite structures ensures malleability and flexibility that could permit the deposition of thin films on flexible substrates [26].
Regardless of the excellent properties and high efficiencies, the poor stability of organic–inorganic perovskite materials are yet a serious challenge, inhibiting PSCs from being commercialized. To be marketable for commercial purposes, PSCs need to be capable of work constantly for over 20 years under outdoor conditions. Thus, large consideration has recently been centered to overcome barriers associated with stability and environmental compatibility of perovskite materials [10].
Presently there is a debate on the use of lead (main component) in PSCs, which causes toxicity problems during device manufacture, placement, and disposal. Hence, the toxicity of lead-based perovskites is an obvious problem due to leaching of lead into the environment [9]. Lead toxicity has been pointed out as one of the most challenging barriers towards the commercialization of solar cells, as compared to stability issues and cost-effective production ways. The environmental impact benefits of lead-free (or lead-reduced) solar cells have been analyzed by Life Cycle Assessment (LCA) [15].
Up to now, several research groups have ambiguously proven their solution to this challenge. Thus, it is critical to test alternatives to attain similar optical and photovoltaic performances for the commercialization of PSCs. Several research groups have tried to replace lead with other elements (Sn, Ge) and organic cations with inorganic cations to form new appropriate non-toxic and stable perovskite materials, which may be a long journey before the final commercialization of PSCs [9].
It is worth studying alternatives using lead-free PSCs, but Lead-free PSCs reached a PCE of only 6% at a time when lead-based PSCs produced efficiency of 17%. Moreover, the Sn-based solar cells display poorer stability than Pb-based solar cells. [14]. Bivalent Sn is the most favorable choice for replacing Pb as they both are in the same group and possess analogous lone-pair s orbitals [10]. Both Sn- and Pb-based materials have a tetragonal structure under ambient conditions; however, Sn-based perovskite have a higher symmetrized α phase as compared to the Pb-based materials lower symmetrized ß phase [47]. Chung et al. [54] first demonstrated CsSnI3 as a solid electrolyte in DSSCs. Afterward Chen et al. [58] fabricated a photovoltaic device, ITO/CsSnI3/Au/Ti, attaining very low PCE of 0.88%. However, Sn2+ based perovskite undergoes oxidation from Sn2+ to Sn4+, which is destructive for the charge transport properties, and PCE. Recently, Lv 2019 [59] reported the replacement of spiro-OMeTAD by a Zn-derivative porphyrin in a lead-free solar cell has resulted in stability up to 60 h for water and 100 h for thermal stability.
There is another approach of mixed Pb/Sn perovskite Solar cell have also been reported. Lead and tin were revealed to be arbitrarily spread in the [MX6] octahedra in the perovskite and percentage of tin could be altered from 0 to 1 [15]. These devices presented the best photocurrent at a 50% mixing ratio. SnO used as ETL has also resulted with good PCE of (13%) and stability (>700 h storage) [15, 60]. LCA showed the replacement of lead did not decrease the environmental impacts, meanwhile the loss of PCE and stability generates an environmental burden. However, those studies are also interesting because they draw consideration to other toxicity problems occurring from the solvent use during processing of charge transport layers (ETLs) [15].
For lead-free inorganic perovskites Tetravalent cations have also been thought to replace Pb. A new chemical formula of A2BX6 structure is designed by eliminating half of the B-site ions in the ABX3 perovskite for adjusting the heterovalent cation substitution as shown in Figure 1. Due to the lack of connectivity in the [BX6] octahedral structure, the A2BX6 can be considered as a 0D non-perovskite which results in different optical and optoelectronic properties of the A2BX6 from those of the ABX3. [3, 9, 10]. Amongst the A2BX6 perovskites, Cs2SnI6, Cs2TiBr6 and Cs2PdBr6 have been employed in photovoltaic devices [9, 10]. Chung et al. [54] first utilized this material as a solid hole transport material in DSSCs.
Furthermore, a special concern for toxicity must be upraised during experimental work in the laboratory, since hazards arise primarily by the absorption of the toxic lead when used in solution, which is significantly higher, particularly through the dermal and respiratory routes; some of the lead derivatives are soluble both in water and fat, posing a high risk. Solvents such as dimethylformamide (DMF) and dimethylsulfoxide (DMSO) are not only toxic, but also raise the risk of bio incorporation as they are miscible in all ratios with water. Thus, these solvents have also been considered as a major contributor to environmental impact [61].
Perovskite solar cells (PSCs) have been established with promising PCEs. Regardless of the great potential as PV material in terms PCE, the instability of the PSCs is one of the core barriers for larger scale applications [8, 9, 39]. At present, PSCs can only perform for several months under active conditions, whereas traditional silicon cells can operate for more than 25 years. Therefore, stability issues must be reasonably dealt with before its actual use and commercialization [62]. Poor stability of PSCs is due to several affiliated factors resulting from exposure to moisture, oxygen, light, and heat [63, 64].
Nevertheless, the importance of stability has been highlighted and recognized as the foremost problem, in the past five years to solve for the perovskite solar cells (PSCs) to be able to challenge in the market arena. So, how to increase the stability of perovskite solar cells is the most significant issue in this field [15].
In this section, the effect of environmental factors will be discussed on PSCs along with approaches developed to improve stability of perovskite solar cells.
The first environmental factor observed to degrade perovskites was Moisture/water. The instability of perovskite at high humidity is the serious issue that needs to be focused. Solar cells when exposed to moisture (water), due to the hygroscopic nature of the organic components of perovskite materials are spontaneously affected by moisture access and then degrade [62]. It has basically been supposed that moisture-induced degradation is the leading issue, imitating MNH3PbI3 stability under ambient conditions.
Prolonged exposure of perovskite material to water vapor activates an irreversible degradation which eventually leads to transformation of the perovskite back to the initial precursors (such as PbI2). In detail, perovskite forms hydrate complexes with water such as (CH3NH3)4PbI6·2H2O and leaves out PbI2, which tend to crystallize, forcing the forward reaction. Moreover, MA+ is slightly acidic and reacts with water to form volatile methylamine (CH3NH3) and hydroiodic acid (HI), according to the following reaction (1): [63].
Some researchers have reported that the compositions, microstructures (such as grain size) also affected the moisture stability of perovskite devices and concluded that larger grains resulted in a smaller area density of grain boundaries, which can be correlated with the improved stability [65].
In demand to progress the chemical stability of MAPbI3-based PSCs against moisture, scientists have proposed replacing the organic cation MA+ with alternative components at the A position. For example, FAPbI3 has been presented to be further thermally stable than MAPbI3 because of its larger tolerance factor. Though, FAPbI3 suffers a phase transition from the a-FAPbI3 (black triangular) phase to the d-FAPbI3 (yellow hexagonal) phase due to the presence of moisture. Furthermore, degradation of FA0.9Cs0.1PbI is prevented by adding a small amount of cesium (Cs) into orbital lead-iodine to form FA0.9Cs0.1PbI in high humidity environment [33].
Smith et al. [66] discussed that Low-dimensional 2-D perovskites exhibited better moisture stability than 3D perovskites due to the hydrophobic nature of organic cations. Though, the insulating aspect of the organic cations with poorer charge transport resulted in lower PCE as compared to 3D perovskites. Therefore, various efforts have been made to form a quasi-2D (or 2D–3D mixture) and 2D on top of 3D (2D@3D) to use the benefits of both 2D and 3D perovskites. The use of 2D perovskite is mostly to improve the moisture stability, a thin 2D layer was deposited on top of 3D MAPbI3 perovskite to cover it fully and shield the 3D perovskite from moisture. The highest PCE for 2D@3D perovskite solar cell was observed to be of 18.0%, with an enhanced device stability under both inert (90% of initial PCE for 32 d) and ambient conditions (72% of initial PCE for 20 d) without encapsulation.
Polymers, such as poly(4-vinylpyridine) (PVP), poly (methyl methacrylate) (PMMA) covering p-type and n-type semiconductors, or insulators, were also reported to improve stability. These long chain polymer acts as defect passivator and a moisture blocker by forming a network along perovskite grains and resulted in improved device efficiency and stability [58, 60, 64].
Light-induced perovskite solar cell degradation and environmental stability are the most frequently cited villains. Early on, stability of PSC was a big issue. But just as there were quick improvements in efficiency of PSCs, there has also been similar quick progresses in stability. Ultraviolet light (UV) can also cause the degradation of MAPbI3 perovskite. For e.g. the commonly used TiO2 electron transport layer (ETL) for these PSCs is responsible for UV-induced degradation. According to the international standards for climate chamber tests (IEC 61646), solar cells need to tolerate long-term stability at 85°C.
Bryant et al. [67] demonstrated that contact of MeNH3PbI3 films to both light and molecular oxygen can initiate quick degradation. Particularly, this reaction is started by the deprotonation of the methylammonium cation of the perovskite by a photogenerated reactive oxygen species (superoxide, O2−). The stability of MeNH3PbI3 based devices was checked under different operating (e.g. light and dark) and environmental conditions and infer that oxygen induced degradation, is relatively dominant than moisture induced degradation and limits the working stability of MeNH3PbI3 containing devices under ambient conditions. Moreover, they pointed out that this fall in device performance can be reduced by the addition of electron acceptor layers within device architecture. Such layers are exposed to augment electron extraction from the absorber (perovskite material) before they react with oxygen, hence decreasing the amount of superoxide O2− and increasing the device stability.
It was noticed that by replacing MA with Cs and FA resulted in improved photostability of the PSCs. By systematically monitoring the development of PL intensity of perovskites, light-induced formation and annihilation of defects were reported to induce photo-instability [68]. Photostability can be improved through defect control by passivating which acted as a defect reservoir on the surface and grain boundaries. To stabilize surface defects, polyethylene oxide was applied and thus improved photostability was achieved. By substituting MA with FA, the degradation became slow with small pores forming on the surface after exposure to light. Moreover, Addition of Cs into the MAFA (forming CsMAFA) further lessen the degradation. XPS, XRD, Fourier transform infrared (FT-IR) spectrometry, and ultraviolet-visible absorption spectrometry were used to investigate the variation of MAPbI3 films under illumination. The result showed that light induced degradation is the main cause of degradation. Using polymer such as PTAA (Poly(triarylamine)) as the HTM, it was observed that pure MAPbI3 devices retained nearly 100% of their initial efficiency after 1000 h aging under constant illumination at room temperature. PTAA which act as a protection layer, inhibited the discharge of gaseous degradation products enhanced stability. However, for devices using Spiro as the HTM, their stability under illumination was lesser than that using PTAA [69, 70].
Heat is also another factor that influences stability due to the inherent matter with low formation energies, and perovskites thus have a great response to a small increase in external temperature [71]. Organic-inorganic perovskites tend to decompose due to the instability of organic A+ cations under thermal atmosphere. Commercial solar cells should be able to work efficiently above 85°C, to have any influence in the market.
MAPbI3 is basically unstable upon thermal stress which produces a discharge of I2 and the presence of metallic Pb at 40°C in the dark [63]. This is produced by the decomposition reactions (2) and (3):
Although reaction (3) is reversible at just 80–85°C, methylammonium iodide decomposes into more volatile compounds as represented by reactions (4) and (5):
It was found that HI(g) and CH3NH2(g) were dominant products during the decomposition of MAPbI3 and only trace amounts of CH3I and NH3 were found. Though, the ratio of CH3I and NH3 increased at higher temperature and lesser than HI(g) and CH3NH2(g). In short, HI(g) and CH3NH2(g) were the dominant decomposition products at ambient temperature under vacuum while CH3I and NH3 gases were obtained at high temperature. Both processes occurred simultaneously near ambient temperature in vacuum and the later was favored at high temperature.
To find out the decomposition temperature of perovskites, Thermogravimetric analysis (TGA) was used. From the mass loss of TGA curve for MAPbI3, the decomposition onset temperature was found to be 234°C [62]. This indicates that as the practical application temperature usually is less than 100°C, so this high decomposition temperature made the stability of MAPbI3 not a big issue. The as prepared film did not show any changes in XRD patterns when stayed inside the vacuum for up to three days. This might be owing to the purer perovskite films without any exposure to the ambient atmosphere. Though, the commonly degradation of the perovskite solar cell was apparent even with encapsulation. This could be inadequate to estimate the long-term stability of a photovoltaic material, which is essential to work for a long time at temperatures lower than the decomposition temperature [72]. The fact that inert condition and encapsulation cannot completely avoid MAPbI3 perovskite degradation. At low temperature, the degradation of MAPbBr3 was found by only releasing HBr and CH3NH2 gases [69]. The encapsulation of devices is essential not only to prevent exposure to oxygen and moisture, but also to avoid leakage of volatile decomposition products. Photostability can also be increased by replacing MA cation with more stable Cs/FA combination.
Substituting organic cations with inorganic Cs+ or Rb+ cations is also valuable to stabilize perovskite solar cells [73, 74]. Grancini et al. [74] stated an ultra-stable 2D/3D (HOOC(CH2)4NH3)2PbI4/CH3NH3PbI3 perovskite, presenting a PCE of 12.9% with carbon electrodes and 14.6% with the normal mesoporous structure and stability of one-year.
By introducing n-butylammonium iodide (BAI) to MAPbI3 perovskite, a mixed 2D (BA)2PbI4 structure is formed, which probably provide an improved protection for the 3D perovskite against heat stress [75]. Octylammonium (OA) cation has also been reported to enhance the thermal stability of perovskites and keep 80% of their initial efficiency for 760 h aged at 85°C in ambient atmosphere without encapsulation [76]. Other additives, such as π-conjugated polymer, nonvolatile ionic liquids, bifunctional hydroxylamine hydrochloride guanidinium isothiocyanate, have also been reported to improve the thermal stability of various perovskites [77, 78, 79].
The discovery and development of organic inorganic perovskite materials have become a hot research topic in the field of photovoltaics. This chapter deals with a comprehensive discussion on the properties and applications of organic inorganic perovskites materials in PSCs. The extraordinarily outstanding performances of organic inorganic perovskites result of their excellent properties. Solar cells based on organic inorganic perovskite materials have achieved much advancement, both in PCE and stability, in a short very time. To PSCs, though great progress has been attained, there are still various obstacles in terms of stability and toxicity until its practical usage in the PV market. However, for large-scale performance, are required to be overcome. So far, great research has been made to overcome these issues by changing the composition of organic inorganic perovskite material either by replacing Pb with Sn or Ge or organic methyl with other organic or inorganic cations. However, commercialization of an organic inorganic perovskite solar cell needs further development in both efficiency and long-term stability, with low-cost photovoltaic materials and ease of printability. To increase stability, various methods such as the use of buffer layers, varying the composition of organic inorganic perovskite materials, and better techniques of encapsulation. In inference, the research which has been enduring for the past five years has attained significant results. Future research needs to endeavor for longer stability with high efficiency.
Primary immunodeficiency (PID) is a large group of rare diseases attributed to inborn genetic errors that impair different components of adaptive and innate immune system, resulting in chronic, serious infections, or other complications. The diseases are often accompanied by a predisposition to autoimmune disorders, autoinflammation, atopy, and malignancy [1, 2, 3, 4]. Unlike secondary immunodeficiency acquired from other diseases or conditions such as malnutrition, immunosuppression, or HIV infections, PIDs are triggered by genetic defects. Based on the abnormality of one or more components of human immunity, PIDs can be divided into antibody deficiencies, combined T- and B-cell deficiencies, deficiencies in the phagocytic or complement system, and immune dysregulation [1]. Diagnosis of these disorders requires good clinical awareness and specialized laboratory testing. Flow cytometry and genetic testing are essential to identify the phenotypic and genetic defects of the diseases and to confirm the diagnosis. Accurate diagnosis and efficient management are important for reducing morbidity and mortality in patients with PID [2]. The chapter provides an overview of the classification and manifestation as well as the diagnosis and management of these disorders.
Individual type of PIDs is considered to be rare in the population; however, recent studies have shown that PIDs may be more common than previously estimated 1% of the population when all varieties are combined [5]. The prevalence of PIDs varies depending on the type of immunodeficiencies and is difficult to be precisely calculated as the number of diagnosed cases is rapidly increasing. A 2018 global survey from the Jeffrey Modell Centers Network (JMCN) reported the case of PID patients followed in the JMCN increased by 35.4% to 102,097, while the case of patients identified with a specific gene defect increased 21.8% to 67,308 during the same period [5]. Up to 2018, 354 distinct disorders with 344 different gene defects were recognized [6]. Of note, most of the cases reported are from developed countries. It is estimated that 70–90% of individuals living with a PID are undiagnosed [7], particularly in the area with poor medical condition and lacking laboratory resources. With the extensive application of exome or whole genome sequencing, it was predicted that the associated PID genetic defects would reach 1000 under current trend in next decade [5]. Table 1 listed the reported number of 18 most common PID defects among 354 inborn errors of immunity [5]. As shown, antibody deficiencies have much higher occurrence rate against other types of the disorders. Studies also showed that the selective IgA deficiency has the highest prevalence worldwide with a range from 1 in 223 to 1 in 1000 depending on ethnic background [8], while severe combined immunodeficiency (SCID), although fatal, is much rarer (1 in 100,000) [9, 10].
Global prevalence of PIDs reported by Jeffrey Modell Centers Network [5].
The classification of PIDs is generally based on the defects of the major components of human immunity, such as innate/adaptive immunodeficiencies, phagocytic deficiencies, complement deficiencies, and immune dysregulation. The classification has evolved over time with more phenotypic and genetic defects identified [4, 11].
The International Union of Immunological Societies (IUIS) expert committee, currently named as Inborn Errors of Immunity Committee, has been responsible for issuing the classification of PIDs every other year from 1970. The complete catalog of classification has now been widely used as a reference by clinicians and researchers. From 2013, IUIS published more user-friendly phenotypic classification in two formats: one is a pdf file, namely clinically oriented phenotype categorization in the Journal of Clinical Immunology, and the other is a csv file containing a comprehensive list of various disorders that can be downloaded from http://www.iuisonline.org [6, 11]. The phenotypic categorization published in the journal has been well designed for clinical use, while the online list contains the most updated information demonstrated in a digital friendly excel format that can be sorted by phenotypic and genetic features, which are very useful for designing sequencing panels, disease code lists, and diagnostic algorithms.
The major category and subcategory of PIDs from the revised 2017 IUIS phenotypic classification are summarized in Table 2.
Patients with PID present highly heterogeneous clinical symptoms with increased susceptibility to infections and other immune complications [12, 13]. Recurrent infection is the hallmark of the PIDs although a variety of other clinical manifestations may appear before the infection [13, 14]. In fact, noninfectious manifestations, such as gastrointestinal disorders, hematological diseases, autoimmune/autoinflammatory conditions, atopy or malignancy, can be the predominant clinical presentations in some patients with underlying immunodeficiency [3, 15]. Furthermore, patients with PID also demonstrate overlapping symptoms and share similarities with many “routine” diseases.
Majority of patients with PID suffer mild to severe or life-threatening infections. The unique clinical characteristics of infections in PIDs are recurring, chronic, and can appear in multiple anatomic sites. Recurrent infections in both the sinuses and the respiratory tract, such as sinusitis, bronchitis, otitis, and pneumonia, are the most frequent symptoms observed in patients with PID [16], while recurrent systemic infections (e.g., meningitis and bacteremia) are also not rare [17, 18]. Patients with SCID may suffer from unusual or opportunistic infections leading to unexpected complications or death [19].
Autoimmune and autoinflammatory disorders are more frequently seen in some categories of the PIDs than in other diseases [20]. The associated conditions in PID individuals may present in a single tissue or organ, such as autoimmune hemolytic anemia, thrombocytopenia, and autoimmune thyroiditis, or affect multiple organs, exemplified by an related vasculitis, or resemble rheumatic symptoms such as (e.g., dermatomyositis, rheumatoid arthritis, and systemic lupus erythematosus) [3, 20, 21]. To note, family members that carry the same gene mutation may present different types of autoimmune/autoinflammatory symptoms, or without such disorders [22]. In comparison with other types of defects, the autoimmune presentations are relatively common in PIDs with antibody deficiencies (e.g., CVID, selective IgA deficiency), and absence of initial components (C1–C4) of the classical complement system [23, 24].
Patients with PID, particularly infants and young children, may manifest chronic diarrhea, malnutrition, and malabsorption. Some individuals may undergo infections in gastrointestinal tract, such as chronic giardiasis and rotavirus [25], while others may experience a variety of autoimmune or autoinflammatory disorders including inflammatory bowel disease, atrophic gastritis with pernicious anemia, or gluten-sensitive enteropathy [20].
Hematological disorders, such as autoimmune hemolytic anemia, and/or neutropenia and/or thrombocytopenia, are also frequently seen in patients with CVID or selective IgA deficiency [26]. Patients with the Wiskott-Aldrich syndrome, a disease characterized by variable defects in B- and T-lymphocyte function, can present with reduced platelet volume and significant thrombocytopenia [27].
PID patients may also present with a syndrome complex. For example, recurrent bacterial/fungal infections and chronic inflammation of the gastrointestinal and respiratory tract often present in patients with chronic granulomatous disease, while an individual suffering from Wiskott-Aldrich syndrome may have manifestations of eczema, recurrent bacterial infections, autoimmune disorders, and thrombocytopenia [27]. In addition, congenital heart disease and hypocalcemic tetany frequently appear in a newborn baby with the DiGeorge syndrome [28, 29]. In fact, the investigation of patients with a syndrome derived from immunodeficiency may trigger an early diagnosis of PID before the typical immunodeficiency symptoms appear [4].
Compared to individuals with a healthy immune system, patients with PID are expected to have higher prevalence and/or broader spectrum of malignancies [30]. A study showed that lymphoma, the most common malignancy seen in PID patients, has increased 10-folds in male and 8.34-folds in female compared to age-matched controls [31]. Other types of cancer with higher frequency in PIDs are leukemia, digestive tract cancers, and virus-induced cancers [30]. Interestingly, the four most common cancers routinely occurred in men and women (lung, colon, breast, and prostate cancers) do not have significant elevation in subjects diagnosed with PID [31]. Evidence also demonstrated that patients with specific forms of immunodeficiency caused by highly penetrant gene defects have higher risk of developing cancer [32].
Early diagnosis of PID is critical for reducing morbidity or mortality and improving treatment outcomes. Review of clinical and family history and physical examination are the first steps in evaluating the need for further laboratory investigation.
The differentiation of PIDs from other medical conditions can be complicated as the symptoms of infection (e.g., sinusitis, bronchitis, pneumonia, gastroenteritis, meningitis, or sepsis) and other manifestations often present in patients with non-PID. Hence, it is important to delineate the infectious organisms, the pattern of infections, and clinical pictures for guiding the clinical judgment, prior to focusing on laboratory testing.
Due to the highly variable clinical presentations and low frequency of the PIDs, the diagnosis of patients is often delayed for years. To raise clinical awareness, JMCN has promoted 10 warning signs for children and adults (Table 3). Patients presenting with two or more of the clinical warning signs should be prompted for further investigation for the possible underlying immunodeficiencies and referred to immunologists for proper disease management.
Clinical warning signs of PIDs.
The laboratory testing is essential to diagnose and delineate the immunologic defects of PIDs. Patients with clinical suspicion should be further investigated for the response of innate immunity and adaptive immunity [33, 34]. Table 4 listed the most common tests used for initial screening of PIDs.
Measurement of serum immunoglobulins is the first-line test for evaluating B-lymphocyte functions. Quantitative measurements of IgG, IgA, IgM, and IgE will identify either hypogammaglobulinemia or deficiency of an individual class of immunoglobulins. Evaluation of IgG subclasses may be required when a patient has strong implication of humoral immunodeficiency but the total IgG is normal. To be mindful, the results of immunoglobulin quantitation must be interpreted with appropriate age-specific ranges. Assessment of antibody responses to immunization with protein antigens (e.g., tetanus or diphtheria toxoids) and polysaccharide antigens (e.g., pneumococcal capsular) is another way to evaluate humoral immunity, although note is to be taken that live viral vaccines must be restricted to a patient with underlying immunodeficiency [35].
Delayed-type hypersensitivity (DTH) skin test is commonly used to screen whether the patient has intact cell-mediated immune response. A positive DTH skin test generally rules out the possible defect of cellular immunity [36]. Nevertheless, the test requires that individuals must have sufficient prior exposure and sensitization to the testing antigen; therefore, it may not be suitable for infants and young children. Quantitation of T-lymphocytes (CD3, CD4, CD8) in peripheral blood is able to indirectly reflect the aberrant cellular immunity and can be easily performed by flow cytometry. More specialized T-cell function tests would provide in-depth information in immune system, which include the assessment of lymphocyte proliferation in response to stimulus such as mitogens (e.g., phytohemagglutinin, ConA, and PMA), or specific antigens (e.g., candida). Furthermore, in vitro measurements of intra- and/or extracellular cytokine responses (e.g., interleukin 2, interferon-gamma, BAFF, and TNF) are informative for the investigation of T- and B-lymphocyte regulation [37].
Leukocyte count and differential can assess the phagocytic disorders such as congenital agranulocytosis or cyclic neutropenia. Phagocytic function can be indirectly assessed by traditional nitroblue tetrazolium (NBT) assay, which measures phagocytic cells’ killing capability in response to an oxidative burst. More recently, a simpler dihydrorhodamine 123 (DHR) assay based on flow cytometry has replaced NBT test for assisting the diagnosis of chronic granulomatous disease (CGD), Rac2 deficiency, and complete myeloperoxidase deficiency [38, 39]. Other complicated in-vitro functional methods such as the measurement of directed cell movement (chemotaxis), ingestion (phagocytosis), and intracellular killing (bactericidal activity) are available in some specialized laboratories [40].
The importance of evaluating NK cells in human immunity has been previously underscored, and this is supported by two evidences: significantly increased number of patients with reduced NK cells and/or functions, and over 40 genetically defined congenital immunodeficiencies present with impaired NK cell functions [41]. There are several methods utilized for the examination of NK cell functions including 51chromium release assay, flow cytometry-based perforin/granzyme expression and CD107a degranulation. These assays are particularly valuable for the patients suspected of primary hemophagocytic lymphohistiocytosis [42, 43].
The complement system can be evaluated by measuring the level or function of complement proteins that are involved in the classical and alternative activation pathways. C3 and C4 are the complements routinely tested. Quantitative and functional assay of C1 esterase inhibitor is essential for the diagnosis of hereditary angioedema. Assays of CH50 and AH50 are, respectively, used to measure the overall complement activity in the classical or alternative pathway. Combining the results of CH50 and AH50 is indicative for further investigation of individual complement proteins that initiate the classical or alternative pathway or common terminal pathway [44].
As our understanding of the defect or dysfunction of immune system increases, immunophenotypic and functional assays based on flow cytometry have been extensively used in identifying the abnormality of various cell types and their functions associated with certain diseases, including PIDs. Furthermore, flow cytometry is also a favorable technique for the measurement of intra- and extracellular cytokine production (e.g., IL12, IFN, TNF, and TH17), cell surface protein expression (e.g., Foxp3, CTLA-4, and BTK), and cellular signaling pathways (e.g., phosphor-STAT) [45]. The information gained from flow cytometry analysis can assist not only in the diagnosis, monitoring, and treatment of the diseases but also in understanding the influence of immune system associated with genetic defects that are newly identified. Table 5 lists the flow cytometry assays used for common PID disorders. Most of the tests listed are required to be undertaken in a specialized laboratory, with the exception of TBNK cell populations, memory B cells, and some function assays that can be performed in a routine diagnostic laboratory.
Initial laboratory tests for PIDs.
Proper instrument setting, standardized operating procedures, and good quality controls must be exercised when performing flow cytometric analysis, as flow cytometry is susceptible to assay variation,. The reported data must include both percentage and absolute number of specific cell population. Moreover, appropriate age-matched reference ranges should also be provided in the final report [47, 48]. Ideally, each laboratory should establish their own normal ranges, but this is often not feasible; alternatively, published reference ranges may be used if a proper validation has been undertaken.
To date, flow cytometry has also been widely used for evaluating cell functions. Traditionally, lymphocyte functions were tested by radioactive methods, such as cytotoxicity of T and NK cells (chromium release) or proliferation of T cells (tritiated thymidine uptake). These approaches are still recognized as gold standard by some clinicians. However, radioactive methods have the following intrinsic limitations: involvement of radioactivity, labor intensive, high expertise required, and poor result reproducibility. Additionally, seeking for a consistent healthy fresh blood as assay normal control and obtaining a proper reference range can be challenging in routine laboratory practice. Therefore, they have been gradually replaced by other methodologies, such as bioluminescence-based assay or flow cytometry–based assay, which use specific dye for the detection of cell proliferation (e.g., CFSE, PKH-2, or PKH-26) or cell death (e.g., 7AAD and Annexing V) [49]. Many assays based on flow cytometry have been increasingly popular as they are easier to perform, have quicker turnaround time, are nonradioactive, are capable of using whole blood, and are more robust compared to the traditional radioactive assays.
Genetic testing plays a critical role in patients with PID in confirming diagnosis, predicting the prognosis, assessing the influences of genotype-phenotype associations, and family planning [50, 51]. Besides, early and accurate molecular diagnosis is vital for guiding the selection of appropriate treatment including genetic therapy. Several molecular tests are available in identifying the genetic defects of PIDs, such as chromosomal analysis, fluorescence in situ hybridization, chromosomal microarray, single gene by Sanger sequencing, gene panels by massively parallel, whole exome, and genome by next-generation sequencing [52]. The selection of these assays should consider their inherent advantages and limitations [50, 53]. The summary of these tests is shown in Table 6. Recent emerged simple molecular assays for measuring circular DNA segments namely T-cell receptor excision circles and kappa-deleting recombination excision circles, based on quantitative PCR amplification of DNA extracted from dried blood spots, enable for a quick screening of newborn SCID [54].
The choice of specific gene(s) for examination is suggested by the patient’s clinical history and phenotypical and functional results. Clinicians are required to have a basic understanding of the utility, accessibility of different genetic approaches. The selection criteria of molecular methodology should be based on the greatest odds of achieving the diagnosis within an acceptable time frame with the most cost-effective test. There is no specific algorithm for genetic testing in patients with PID as individual’s genetic mutation is often unique, the technology, cost, and the assay turnaround time are constantly changing, and each molecular method has inherent advantages and limitations. Practically, two or more approaches are often used together to achieve an optimal diagnosis [50]. For example, single gene Sanger sequencing is considered to be not only a simple and reliable assay for testing patients with known monogenic mutations of PID or their family members, but it can also serve as a tool for confirming the genetic variants detected by whole exome sequencing. When assessing large numbers of mutations, gene panels or whole genome/exome approach may be more cost-effective and faster than single gene analysis. Since genetic testing in primary immunodeficiency is highly personalized, and a specific genetic mutation does not always translate into a disease, test results must be interpreted with caution by genetic consultants and immunologists.
The recent advances of sequencing technologies have facilitated the genomic assays to become the standard of care in some hospitals although these techniques may face the challenges of cost, accessibility, and interpretation issues. The exponential growth of genetic analysis by next-generation sequencing and other novel molecular technologies has enabled quick identification of known and novel mutations, which contributed to a dramatic expansion of the number and types of PIDs [16, 53, 55].
Treatments for PIDs involve preventing and controlling recurrent infections, treating symptoms, strengthening the immunity, and treating the underlying cause of the immune defects. Illness associated with PIDs such as autoimmune disorders or malignancies should also be managed [1, 13].
More aggressive and/or longer course of antibiotics than “normal infections” is usually prescribed in patients with PID, in order to control the infections caused by bacteria or fungi. Some patients may require prolonged antibiotic therapy to prevent infections and permanent damage to organs [13]. Routine immunizations can also provide protective immunity to those at risk of infections, but the attenuated vaccines such as oral polio and measles-mumps-rubella might not be suitable for children with PIDs. For viral infection, interferon-gamma therapy may be of choice besides other antiviral drugs routinely used (e.g., amantadine and acyclovir) [13]. In patients with chronic granulomatous disease, using granulocyte colony–stimulating factor, a glycoprotein that is able to stimulate the proliferation/differentiation and improve the functions of neutrophil, can help increase the levels of immune-strengthening leukocytes to control the infections [56].
Immunoglobulin replacement has been the pillar of therapy for recurrent infections of PIDs, since around 60% of PID cases have impaired antibody production [57]. In fact, most of these patients will require life-time immunoglobulin replacement therapy. Immunoglobulin can be delivered either intravenously (abbreviated IVIG) or subcutaneously (abbreviated SCIG). The choice of which route depends on the circumstance although both of them have been demonstrated to be effective. Because higher IgG levels can be obtained through intravenous administration, IVIG has been routinely used for preventing serious/recurrent infections [58]; however, SCIG has recently emerged as a popular route for delivery due to its fewer side effects and greater flexibility [57, 59]. Future research direction is focusing on more precise IgG replacement in PIDs, such as the development of IgG subclass-specific enriched preparation and microbe-specific IgG [58].
Apart from controlling infections, the considerable morbidity and mortality caused by noninfectious complications of PIDs can also be troublesome to clinicians. To standardize clinical practices and improve treatment outcome, British Society of Immunology has recently published the first set of recommendations for monitoring and managing the noninfectious complications of CVID [60].
Bone marrow transplantation (BMT) and hematopoietic stem cell transplantation (HSCT) are feasible options for a permanent cure for several types of life-threatening immunodeficiency, with SCID in particular [61, 62]. Immune system can reconstitute when stem cells harvested from bone marrow or cord blood are transferred to the patients with PID. However, the successful rate of biological match, possibility of life-threatening graft-versus-host-disease, and the risk of uncontrolled infections following the destruction of the patient’s own immune system prior to the transplant should be well evaluated.
The technical advances of genetic engineering provide another hope to cure PIDs. Substantial progress has been made in the past decade in treating several types of PIDs (e.g., adenosine deaminase-SCID, SCID-X1, chronic granulomatous disorder, and Wiskott-Aldrich syndrome) with gene therapy [63, 64, 65]. Current treatment scenario is mostly based on ex-vivo deliver of therapeutic transgene through viral vectors to autologous stem cells, followed by transplantation back to the same patient. Although the overall outcome from all the clinical trials targeting different PIDs has been extremely promising, however, serious adverse events (e.g., vector-mediated oncogenesis) and high cost may be a hindrance to clinical trials and promotion of gene therapy [63, 65]. A summary of current strategies for treatment and management of PIDs is shown in Table 7.
The prognosis of patients with PID is extremely variable depending on the type of immune defects. Infants with SCID will die in the first 2 years of life without HSCT/BMT or gene therapy. Individuals who obtained stem cell transplantation in early childhood (before 3.5 months) have better prognosis [67]. Many PID patients who received proper medical care and treatments are able to live healthy and independent life for a long term. With the enhancement in managing infections and other complications and growing application of definitive therapies, the outcomes and long-term survival of PIDs have improved dramatically since the 1970s [13].
The investigation of PIDs has provided valuable insights to understand the specific gene defect that impairs the immune system. Flow cytometry and genetic testing enable to identify existing and novel phenotypes and genotypes as well as their impact on PIDs. The applications of flow cytometry and genetic technologies have expanded dramatically with more types of PID is defined, and the use of mass sequencing technologies has accelerated the identification of novel disorders. To efficiently use these complex assays, clinicians should have a good understanding of these methods and know how to interpret the results for diagnosis and disease management [33].
The management of patients with PID is based on three aspects of diagnosis: suspicious clinical manifestations, aberrant results of immune response, and the underlying genetic defect [4]. However, the diagnosis of PIDs may confront significant challenges: there are large numbers of variable types of PIDs to be recognized and most of them have alike clinical presentations with common diseases; immunodeficiencies derived from multiple gene defects can share similar symptoms, and a defect in the same gene may have various clinical manifestations [1]. While severe forms of PIDs are relatively easier to be recognized, milder immunodeficiencies may not raise alertness until typical presentation occurs [68, 69]. Additionally, the criteria for constituting a PID diagnosis are subjective, for example, the degree of frequency and the severity of the infections for establishing the diagnosis are unclear, the association of PIDs with autoimmune disorder or malignancy is ambiguous, and some individuals may not have noticeable symptoms apart from laboratory findings. Furthermore, advanced laboratory examination such as specialized flow cytometric and genetic analysis is not always easy to access. All these factors may contribute to delayed or missed diagnosis of the diseases.
To combat the challenges, clinical warning signs of PIDs should be disseminated to all clinicians for raising earlier recognition of the diseases, and an immunologist must be consulted for proper diagnosis and management. Due to the complexity of clinical presentations and large number of disease types, the use of scoring system based on the codes of the international classification of PIDs [69] assisted by artificial intelligence may be beneficial for clinicians to differentiate these disorders from other diseases and raise initial recognition. The recent advances in understanding the human immune system, development of novel cellular and molecular assays, and collaborations from the international/national organizations have led to significant increase of clinical awareness and cases diagnosed and improvement of disease management and treatment outcomes for PIDs.
The author thanks Dr. Alexander Richardson from the Royal College of Pathologists of Australasia for assisting the references work and Mrs. Xiumei Wei from the Sutherland Centre of Immunology in NSW, Australia, for valuable opinions.
The author declares that there is no conflict of interest.
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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In such cases, the said graph theory and matrix method provides very suitable and fruitful solutions to make the decision to its final effective extent. The further improvements and the outcome enhancement can also be revealed through the use of combined practice of graph theory results along with some artificial intelligence-inspired logics and practices such as fuzzy logic, artificial neural network, etc. The significance and applicability of said method in vast fields of science, engineering, and research are also proved. Nowadays, our manufacturing sectors are getting up to date through the applications of artificial intelligence and several software-based directions. This is all to enhance the overall machine system performance with a view to improve desired performance characteristics of the process under the study. 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The use of clinical DSS in AF management is ubiquitous, starting from detection of AF through sophisticated electrophysiology treatment procedures, all the way to monitoring the patient's health during follow‐ups. Most of the software associated with AF DSS are developed based on signal processing, image processing, and artificial intelligence techniques. The chapter begins with a brief description of DSS in general and then introduces DSS that are used for various clinical applications. The chapter continues with a background on AF and some relevant mechanisms. 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The prosthesis design, control, and architecture completely changed with the change in the amputation level. The transradial amputee stump design, electronics, battery, and circuit placement change significantly with the change of the residual arm of the amputee. This leads to designing the prostheses with the focus of the amputation level and ease of customization. Recent development in the 3D printing and open source prosthetic design leads the user to choose, modify, and print the prostheses with the required sets of functionalities. In this chapter, a brief introduction of the prostheses has been given, starting with the types of prostheses according to the level of amputation and functionality. Then, the state-of-the-art prostheses available commercially and under research will be introduced. Afterward, the 3D printed prostheses are discussed. 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Because this type of comparison is not present in the literature yet, this work wants to place the emphasis on the fact that till now there is not a unique approach to solve problems of geometry assurance and no approach can be defined as better than another, in terms of results.",book:{id:"5379",slug:"computer-aided-technologies-applications-in-engineering-and-medicine",title:"Computer-aided Technologies",fullTitle:"Computer-aided Technologies - Applications in Engineering and Medicine"},signatures:"Andrea Corrado and Wilma Polini",authors:[{id:"16151",title:"Dr.",name:"Wilma",middleName:null,surname:"Polini",slug:"wilma-polini",fullName:"Wilma Polini"},{id:"190416",title:"Ph.D. Student",name:"Andrea",middleName:null,surname:"Corrado",slug:"andrea-corrado",fullName:"Andrea Corrado"}]},{id:"67441",title:"Human-Computer/Device Interaction",slug:"human-computer-device-interaction",totalDownloads:764,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Any interaction refers to the communication between two or more entities (be it abstract/conceptual or physical entity). Successful interaction is equated from the properties of each entity involved in the interaction as well as the capabilities of the interacting entities. With the diversified use and application of computers and specialized devices for specific tasks, such as biomechanical and biomedical devices, interaction design needs to further study the context of the tasks as well. Moreover, with the inclusion of embedded systems and smart devices, instead of focusing only on the hardware performance, the computer architecture needs to consider the opportunities. Especially, HCI can be improved as the current technologies are giving an opportunity for building smart interaction where the user interacts with devices implicitly and in less obtrusive way. In light of this, the design and architecture of an engineered product need to strive for making the product usable and used while making it useful to the user. And this can be achieved if interaction design is dictated by scrutinizing the user model with respects to the usability attributes in view of the context of its task as well as the platform capabilities and constraints as discussed in this chapter.",book:{id:"8347",slug:"computer-architecture-in-industrial-biomechanical-and-biomedical-engineering",title:"Computer Architecture in Industrial, Biomechanical and Biomedical Engineering",fullTitle:"Computer Architecture in Industrial, Biomechanical and Biomedical Engineering"},signatures:"Dagmawi Lemma Gobena",authors:[{id:"284850",title:"Dr.",name:"Dagmawi Lemma",middleName:null,surname:"Gobena",slug:"dagmawi-lemma-gobena",fullName:"Dagmawi Lemma Gobena"}]},{id:"67484",title:"Human Behavior Modeling: The Necessity of Narrative",slug:"human-behavior-modeling-the-necessity-of-narrative",totalDownloads:932,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"As progress is made in the development of artificial intelligent mechanisms to assist human research into aspects of industrial, biomechanical and biomedical engineering, the conceptualization of mental behavior of human entities become more vital and more central to the success of any interaction between machine and humans. This discussion explores one of the most important features of human behavior, the fundamental and irreversible concept of narrative. The narrative is the essential construct for the theoretical understanding and presentation of human communication, including formal and informal logic, emotional wonder and desperation, noble and selfish biases, nationalism and globalist politics, and any form of spiritualism. This presentation offers a working definition of human narrative and proposes its basic structure that must be represented by any computer system which is required to deal with human behavior.",book:{id:"8347",slug:"computer-architecture-in-industrial-biomechanical-and-biomedical-engineering",title:"Computer Architecture in Industrial, Biomechanical and Biomedical Engineering",fullTitle:"Computer Architecture in Industrial, Biomechanical and Biomedical Engineering"},signatures:"Roger Parker",authors:[{id:"284043",title:"Ph.D.",name:"Roger",middleName:null,surname:"Parker",slug:"roger-parker",fullName:"Roger Parker"}]},{id:"66967",title:"Decision-Making in Real-Life Industrial Environment through Graph Theory Approach",slug:"decision-making-in-real-life-industrial-environment-through-graph-theory-approach",totalDownloads:841,totalCrossrefCites:9,totalDimensionsCites:9,abstract:"The approach called as “graph theory and matrix approach” has been well employed in numerous research studies with a view to perform the decision-making while the situation is becoming perplexed type or where there is a very strong relative importance of one parameter over another. In such cases, the said graph theory and matrix method provides very suitable and fruitful solutions to make the decision to its final effective extent. The further improvements and the outcome enhancement can also be revealed through the use of combined practice of graph theory results along with some artificial intelligence-inspired logics and practices such as fuzzy logic, artificial neural network, etc. The significance and applicability of said method in vast fields of science, engineering, and research are also proved. Nowadays, our manufacturing sectors are getting up to date through the applications of artificial intelligence and several software-based directions. This is all to enhance the overall machine system performance with a view to improve desired performance characteristics of the process under the study. Few sections of this chapter has also elaborated the utility of the artificial intelligence-inspired fuzzy logic-based decision system which has already been a part of previous researches.",book:{id:"8347",slug:"computer-architecture-in-industrial-biomechanical-and-biomedical-engineering",title:"Computer Architecture in Industrial, Biomechanical and Biomedical Engineering",fullTitle:"Computer Architecture in Industrial, Biomechanical and Biomedical Engineering"},signatures:"Ravi Pratap Singh, Ravinder Kataria and Sandeep Singhal",authors:[{id:"265010",title:"Dr.",name:"Ravi Pratap",middleName:null,surname:"Singh",slug:"ravi-pratap-singh",fullName:"Ravi Pratap Singh"},{id:"265017",title:"Dr.",name:"Ravinder",middleName:null,surname:"Kataria",slug:"ravinder-kataria",fullName:"Ravinder Kataria"},{id:"271624",title:"Dr.",name:"Sandeep",middleName:null,surname:"Singhal",slug:"sandeep-singhal",fullName:"Sandeep Singhal"}]}],onlineFirstChaptersFilter:{topicId:"716",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,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:317,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:129,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:105,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:2,numberOfUpcomingTopics:1,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:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. 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She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). 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Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. 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His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. 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She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}]},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null}]},{type:"book",id:"7572",title:"Trauma in Dentistry",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7572.jpg",slug:"trauma-in-dentistry",publishedDate:"July 3rd 2019",editedByType:"Edited by",bookSignature:"Serdar Gözler",hash:"7cb94732cfb315f8d1e70ebf500eb8a9",volumeInSeries:3,fullTitle:"Trauma in Dentistry",editors:[{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. 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