Some electrical properties of solid phase for Sn–41.39 at.% Cd–6.69 at.% Sb, Sn–49 at.% In–1 at.% Cu, Sn–50 at.% Ag–10 at.% Bi, Sn–32 at.% Bi–3 at.% Zn [31].
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5963",leadTitle:null,fullTitle:"Functional Food - Improve Health through Adequate Food",title:"Functional Food",subtitle:"Improve Health through Adequate Food",reviewType:"peer-reviewed",abstract:"In recent years, the concern of society about how food influences the health status of people has increased. Consumers are increasingly aware that food can prevent the development of certain diseases, so in recent years, the food industry is developing new, healthier products taking into account aspects such as trans fats, lower caloric intake, less salt, etc. However, there are bioactive compounds that can improve the beneficial effect of these foods and go beyond the nutritional value. This book provides information on impact of bioactive ingredients (vitamins, antioxidants, compounds of the pulses, etc.) on nutrition through food, how functional foods can prevent disease, and tools to evaluate the effects of bioactive ingredients, functional foods, and diet.",isbn:"978-953-51-3440-4",printIsbn:"978-953-51-3439-8",pdfIsbn:"978-953-51-4718-3",doi:"10.5772/66263",price:139,priceEur:155,priceUsd:179,slug:"functional-food-improve-health-through-adequate-food",numberOfPages:318,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a7e56600bbbb1d3ed63d334cc575dc14",bookSignature:"Maria Chavarri Hueda",publishedDate:"August 2nd 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5963.jpg",numberOfDownloads:35324,numberOfWosCitations:133,numberOfCrossrefCitations:126,numberOfCrossrefCitationsByBook:4,numberOfDimensionsCitations:229,numberOfDimensionsCitationsByBook:6,hasAltmetrics:1,numberOfTotalCitations:488,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 8th 2016",dateEndSecondStepPublish:"November 29th 2016",dateEndThirdStepPublish:"February 25th 2017",dateEndFourthStepPublish:"May 26th 2017",dateEndFifthStepPublish:"July 25th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"150285",title:"Dr.",name:"María",middleName:null,surname:"Chávarri Hueda",slug:"maria-chavarri-hueda",fullName:"María Chávarri Hueda",profilePictureURL:"https://mts.intechopen.com/storage/users/150285/images/system/150285.jpeg",biography:"Maria Chávarri Hueda has received her MS degree in Biological Sciences from Universidad de Navarra, Spain, in 1997. She obtained her PhD degree from Nutrition and Food Science Area, Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country. Chávarri has experience in biotechnology and food science, acting on the following subjects: bioactive molecules and functional activity, probiotics, and nutritional status. She worked on the “Influence of the lipid source of the diet on various aspects of hepatic metabolism of triglycerides and cholesterol.” Over the last few decades, Chávarri worked as a senior researcher at TECNALIA R&I, Technological Development Center, in food and health area, and she has focused her studies on bioactive molecules of food and plant origin and their functional activities, as well as to deepen her knowledge on probiotics, with the objective of developing functional foods.",institutionString:"TECNALIA Research & Innovation",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1130",title:"Euthenics",slug:"euthenics"}],chapters:[{id:"56173",title:"Antioxidant Compounds Recovered from Food Wastes",doi:"10.5772/intechopen.69124",slug:"antioxidant-compounds-recovered-from-food-wastes",totalDownloads:2605,totalCrossrefCites:7,totalDimensionsCites:17,hasAltmetrics:0,abstract:"The increase awareness of nowadays consumers regarding the food they purchase and consume and the health has led to an increase demand of foods containing biologically active compounds, namely antioxidants, which can help the body to fight against oxidative stress. As a consequence finding, new or nonconventional sources of antioxidants are a priority for food and also pharmaceutical industries. Wastes from fruits and vegetable processing are shown to contained valuable molecules (antioxidants, dietary fibers, proteins, natural colorants, aroma compounds, etc.) which can be extracted, purified and valorized in value-added products. The present chapter is underlying the great potential of food wastes to be exploited as sources of antioxidants based on the scientific evidences regarding the possibilities of extraction and purification, health benefits and envisaged applications of antioxidants recovered from these wastes.",signatures:"Sonia Ancuța Socaci, Dumitrița Olivia Rugină, Zorița Maria\nDiaconeasa, Oana Lelia Pop, Anca Corina Fărcaș, Adriana Păucean, Maria Tofană and Adela Pintea",downloadPdfUrl:"/chapter/pdf-download/56173",previewPdfUrl:"/chapter/pdf-preview/56173",authors:[{id:"83458",title:"Dr.",name:"Dumitrita",surname:"Rugina",slug:"dumitrita-rugina",fullName:"Dumitrita Rugina"},{id:"182893",title:"Dr.",name:"Oana Lelia",surname:"Pop",slug:"oana-lelia-pop",fullName:"Oana Lelia Pop"},{id:"191241",title:"Ph.D.",name:"Sonia A.",surname:"Socaci",slug:"sonia-a.-socaci",fullName:"Sonia A. Socaci"},{id:"191607",title:"Ph.D.",name:"Anca C.",surname:"Fărcaş",slug:"anca-c.-farcas",fullName:"Anca C. Fărcaş"},{id:"192098",title:"Prof.",name:"Maria",surname:"Tofana",slug:"maria-tofana",fullName:"Maria Tofana"},{id:"202954",title:"Associate Prof.",name:"Zorita",surname:"Diaconeasa",slug:"zorita-diaconeasa",fullName:"Zorita Diaconeasa"},{id:"202955",title:"Dr.",name:"Adriana",surname:"Paucean",slug:"adriana-paucean",fullName:"Adriana Paucean"},{id:"206132",title:"Prof.",name:"Adela",surname:"Pintea",slug:"adela-pintea",fullName:"Adela Pintea"}],corrections:null},{id:"55271",title:"Polyphenols: Food Sources and Health Benefits",doi:"10.5772/intechopen.68862",slug:"polyphenols-food-sources-and-health-benefits",totalDownloads:2098,totalCrossrefCites:10,totalDimensionsCites:21,hasAltmetrics:1,abstract:"The current scientific knowledge on the relationship between diet and human health is greatly focused on the effects of phytochemicals, especially polyphenols, on chronic diseases, due to their preventive effect as shown by many epidemiological studies. Herbs, cocoa products, and darkly colored berries, such as black elderberries, chokeberries, and black currants, are the richest dietary sources that contribute to the average intake of polyphenols of about 1 g/day. Polyphenols that are the most common in the human diet are not necessarily the most active in the body because their beneficial effects depend on the plant matrix in which they are incorporated and on processing methods and endogenous factors such as microbiota and digestive enzymes. Polyphenol-rich foods are considered as being potential functional foods due to antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, anticancer, vasodilating, and prebiotic-like properties. This review will outline findings on the preventive effects of polyphenols on chronic diseases, the factors affecting polyphenol bioavailability and bioaccessibility, and new trends in functional food production.",signatures:"Nikolina Mrduljaš, Greta Krešić and Tea Bilušić",downloadPdfUrl:"/chapter/pdf-download/55271",previewPdfUrl:"/chapter/pdf-preview/55271",authors:[{id:"190981",title:"Associate Prof.",name:"Greta",surname:"Krešić",slug:"greta-kresic",fullName:"Greta Krešić"},{id:"202696",title:"MSc.",name:"Nikolina",surname:"Mrduljaš",slug:"nikolina-mrduljas",fullName:"Nikolina Mrduljaš"},{id:"205908",title:"Prof.",name:"Tea",surname:"Bilušić",slug:"tea-bilusic",fullName:"Tea Bilušić"}],corrections:null},{id:"55722",title:"Folic and Folate Acid",doi:"10.5772/intechopen.69383",slug:"folic-and-folate-acid",totalDownloads:1831,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Folate is a water-soluble B vitamin, also known as vitamin B9 or folacin. It is found naturally in a wide variety of foods, including vegetables, fruits, nuts, beans, dairy products, meats, eggs, seafood, and grains. However, only about 50% of the folate naturally present in food is bioavailable. Folate is critical in the metabolism of nucleic acid precursors and several amino acids, as well as in methylation reactions. Folic acid helps our bodies produce and maintain new cells, and it helps prevent DNA changes that may lead to cancer. Folate deficiency can cause anemia, insomnia, irritability, depression, Alzheimer’s disease, cardiovascular disease, and more serious health problems. An inadequate folate status during early pregnancy increases the risk of congenital anomalies, such as neural tube defects (NTDs), which are life-threatening and cause life-long disabilities. Therefore, it has been recommended by the U.S. Public Health Service that even before becoming pregnant, women should consume 400 µg of synthetic folic acid daily, whether in the form of foods or supplements, as well as maintain a healthy diet of folate-rich foods to reduce NTD risk.",signatures:"Hiroko Watanabe and Tomoko Miyake",downloadPdfUrl:"/chapter/pdf-download/55722",previewPdfUrl:"/chapter/pdf-preview/55722",authors:[{id:"75055",title:"Prof.",name:"Hiroko",surname:"Watanabe",slug:"hiroko-watanabe",fullName:"Hiroko Watanabe"},{id:"206631",title:"MSc.",name:"Tomoko",surname:"Miyake",slug:"tomoko-miyake",fullName:"Tomoko Miyake"}],corrections:null},{id:"55492",title:"New Advances about the Effect of Vitamins on Human Health: Vitamins Supplements and Nutritional Aspects",doi:"10.5772/intechopen.69122",slug:"new-advances-about-the-effect-of-vitamins-on-human-health-vitamins-supplements-and-nutritional-aspec",totalDownloads:3345,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:1,abstract:"The early twentieth century was a crucial period for the identification and biological-chemical-physical characterisation of vitamins. From then until now, many studies have attempted to clarify into detail the biological role of the vitamins in humans and their direct connection with certain diseases, either in a negative way (appearance of deficiency diseases due to vitamin deficiency) or a positive way (use of vitamins to treat diseases and/or to improve human health). The aim of this work is to analyse, from an integrative point of view, the information about vitamins and their effects on human health, and to identify direct correlations between these compounds and health. The effects of vitamins supplements on diet are also explored. The analysis of the results shows that it is impossible to establish robust and universal conclusions about the benefit of vitamin supplementation on human health beyond the prevention and/or treatment of deficiency states.",signatures:"Noelia García Uribe, Manuel Reig García-Galbis and Rosa María\nMartínez Espinosa",downloadPdfUrl:"/chapter/pdf-download/55492",previewPdfUrl:"/chapter/pdf-preview/55492",authors:[{id:"165627",title:"Dr.",name:"Rosa María",surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa"},{id:"205891",title:"MSc.",name:"Noelia",surname:"García Uribe",slug:"noelia-garcia-uribe",fullName:"Noelia García Uribe"},{id:"205892",title:"Dr.",name:"Manuel",surname:"Reig García-Galbis",slug:"manuel-reig-garcia-galbis",fullName:"Manuel Reig García-Galbis"}],corrections:null},{id:"55507",title:"Fermented Pulse-Based Food Products in Developing Nations as Functional Foods and Ingredients",doi:"10.5772/intechopen.69170",slug:"fermented-pulse-based-food-products-in-developing-nations-as-functional-foods-and-ingredients",totalDownloads:2062,totalCrossrefCites:11,totalDimensionsCites:25,hasAltmetrics:0,abstract:"Pulses play a significant and diverse role in the agricultural systems and diets of underprivileged populations worldwide. They are ideal produce for reducing poverty, improving human health and nutrition, and enhancing resilience of the ecosystem. Fermentation is a processing technique that has been used for decades to transform food produce with improved health, functional, and nutraceutical benefits. In tandem with the United Nations’ (UN’s) sustainable development goal Number 3, fermented food products from pulses with health benefits align with this initiative to end hunger, achieve food security, and improve nutrition. In solidarity with the celebration of International Year of Pulses 2016 (IYP2016) and considering the relative neglect of pulses as compared with other food groups, this chapter would be vital in positioning pulses and fermented products from them as readily available functional foods. With increased interest in fermentation, fermented pulse-based foods have been identified as excellent sources of bioactive and functional foods. Thus, fermented pulse-based products present a viable alternative, relatively available, affordable, and cheap source of foods with properties beyond that of basic nutrition.",signatures:"Oluwafemi Ayodeji Adebo, Patrick Berka Njobeh, Janet Adeyinka\nAdebiyi, Sefater Gbashi, Judith Zanele Phoku and Eugenie Kayitesi",downloadPdfUrl:"/chapter/pdf-download/55507",previewPdfUrl:"/chapter/pdf-preview/55507",authors:[{id:"60387",title:"Prof.",name:"Patrick Berka",surname:"Njobeh",slug:"patrick-berka-njobeh",fullName:"Patrick Berka Njobeh"},{id:"201370",title:"Dr.",name:"Oluwafemi",surname:"Adebo",slug:"oluwafemi-adebo",fullName:"Oluwafemi Adebo"},{id:"201371",title:"Dr.",name:"Eugenie",surname:"Kayitesi",slug:"eugenie-kayitesi",fullName:"Eugenie Kayitesi"},{id:"201372",title:"MSc.",name:"Janet",surname:"Adebiyi",slug:"janet-adebiyi",fullName:"Janet Adebiyi"},{id:"201373",title:"Dr.",name:"Sefater",surname:"Gbashi",slug:"sefater-gbashi",fullName:"Sefater Gbashi"},{id:"201376",title:"Dr.",name:"Judith",surname:"Phoku",slug:"judith-phoku",fullName:"Judith Phoku"}],corrections:null},{id:"55808",title:"The Role of Legumes in Human Nutrition",doi:"10.5772/intechopen.69127",slug:"the-role-of-legumes-in-human-nutrition",totalDownloads:5388,totalCrossrefCites:61,totalDimensionsCites:100,hasAltmetrics:1,abstract:"Legumes are valued worldwide as a sustainable and inexpensive meat alternative and are considered the second most important food source after cereals. Legumes are nutritionally valuable, providing proteins (20–45%) with essential amino acids, complex carbohydrates (±60%) and dietary fibre (5–37%). Legumes also have no cholesterol and are generally low in fat, with ±5% energy from fat, with the exception of peanuts (±45%), chickpeas (±15%) and soybeans (±47%) and provide essential minerals and vitamins. In addition to their nutritional superiority, legumes have also been ascribed economical, cultural, physiological and medicinal roles owing to their possession of beneficial bioactive compounds. Research has shown that most of the bioactive compounds in legumes possess antioxidant properties, which play a role in the prevention of some cancers, heart diseases, osteoporosis and other degenerative diseases. Because of their composition, legumes are attractive to health conscious consumers, celiac and diabetic patients as well as consumers concerned with weight management. The incorporation of legumes in diets, especially in developing countries, could play a major role in eradicating protein-energy malnutrition especially in developing Afro-Asian countries. Legumes could be a base for the development of many functional foods to promote human health.",signatures:"Yvonne Maphosa and Victoria A. Jideani",downloadPdfUrl:"/chapter/pdf-download/55808",previewPdfUrl:"/chapter/pdf-preview/55808",authors:[{id:"201151",title:"Ph.D. Student",name:"Yvonne",surname:"Maphosa",slug:"yvonne-maphosa",fullName:"Yvonne Maphosa"}],corrections:null},{id:"55300",title:"Effect of Bioactive Nutriments in Health and Disease: The Role of Epigenetic Modifications",doi:"10.5772/intechopen.68789",slug:"effect-of-bioactive-nutriments-in-health-and-disease-the-role-of-epigenetic-modifications",totalDownloads:1650,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Recently, a list of clinical, physiopathological, and epidemiological studies has underlined the detrimental or beneficial role of nutritional factors in some chronic diseases such as obesity, type 2 diabetes, cardiovascular disease, and cancer. It has been described that lifestyle, environmental conditions, and nutritional compounds influence gene expression. In the last instance, it has been demonstrated that bioactive nutrimental components are important signal molecules that carry information from the external environment and could affect in biological terms, processes related to gene expression. Bioactive nutriments can work in different ways: regulating the chromatin structure or factors that directly regulate the activity of nuclear receptors. The relevance of the changes in the chromatin structure has been demonstrated by the fact that many chronic diseases and metabolic disorders are related with changes in DNA methylation patterns. For this reason, recently, the bioactive food nutriments have been investigated to characterize the molecular mechanism involved in changes of the chromatin structure, such as acetylation and methylation, and their potential benefit on chronic diseases. The dietary compounds intake involved in the regulation of epigenetic modifications can provide significant health effects and may prevent various pathological processes involved in the development of cancer and other serious diseases.",signatures:"Pablo Bautista‐García, Lorena González‐López, Berenice González‐\nEsparza and Camila Del Castillo‐Rosas",downloadPdfUrl:"/chapter/pdf-download/55300",previewPdfUrl:"/chapter/pdf-preview/55300",authors:[{id:"103258",title:"Dr.",name:"Pablo",surname:"Bautista",slug:"pablo-bautista",fullName:"Pablo Bautista"},{id:"202834",title:"Dr.",name:"Lorena",surname:"González",slug:"lorena-gonzalez",fullName:"Lorena González"},{id:"205614",title:"BSc.",name:"Berenice",surname:"González-Esparza",slug:"berenice-gonzalez-esparza",fullName:"Berenice González-Esparza"},{id:"205615",title:"BSc.",name:"Camila",surname:"Del Castillo-Rosas",slug:"camila-del-castillo-rosas",fullName:"Camila Del Castillo-Rosas"}],corrections:null},{id:"55410",title:"Functional and Biological Potential of Bioactive Compounds in Foods for the Dietary Treatment of Type 2 Diabetes Mellitus",doi:"10.5772/intechopen.68788",slug:"functional-and-biological-potential-of-bioactive-compounds-in-foods-for-the-dietary-treatment-of-typ",totalDownloads:2226,totalCrossrefCites:6,totalDimensionsCites:6,hasAltmetrics:1,abstract:"Type 2 diabetes mellitus (T2DM), or noninsulin-dependent diabetes, is a complex disease characterized by the alteration of oxidoreductive and proinflammatory mechanisms, which leads to disorders in the insulin receptor and consequent chronic hyperglycemia. The hypoglycemic, insulinomimetic, and lipid-lowering potential of food is a reality given the advances in understanding of the role of food in nutrition. Besides its nutritional content, food exerts a biological function in the organism, and this demonstrates the importance of redirecting therapeutic strategies as well as related prevention policies of T2DM. The present review evaluates the effect of food on T2DM treatment. Particular attention is paid to the consumption of nopal, soy, and oats for their hypoglycemic functions, as well as the consumption of omega-3 fatty acids, which are associated with the control of metabolic alterations of this disease.",signatures:"Daniel Pelcastre Monjiote, Edwin E. Martínez Leo and Maira Rubi\nSegura Campos",downloadPdfUrl:"/chapter/pdf-download/55410",previewPdfUrl:"/chapter/pdf-preview/55410",authors:[{id:"201057",title:"Dr.",name:"Maira",surname:"Segura Campos",slug:"maira-segura-campos",fullName:"Maira Segura Campos"}],corrections:null},{id:"55567",title:"Meat Product Reformulation: Nutritional Benefits and Effects on Human Health",doi:"10.5772/intechopen.69118",slug:"meat-product-reformulation-nutritional-benefits-and-effects-on-human-health",totalDownloads:1824,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"This chapter aims to present the current state of the art in the field of meat product reformulation with respect to issues concerning the nutritional improvement and overall health benefits of such products. Our research team has recently finalised a national research project concerning this topic, and we feel that other food scientists could benefit from the theoretical and practical knowledge gathered during this time. The chapter will be divided into four subchapters. The first subsection will present the main targets of meat reformulation, such as lipid or protein profile modification, the use of bioactive compounds as additives, etc. The second subsection will discuss the bioavailability and bioaccessibility of carotenoids, phenolic compounds and other bioactive compounds, presenting these parameters from a nutraceutical perspective. The last subsections will include reported consumer attitudes. In this work, we will present data that could aid scientists in the field of food science to better grasp notions concerning consumer benefit, such as bioavailability, not only of a specific bioactive compound but also as part of a complex food matrix.",signatures:"Elisabeta Botez, Oana V. Nistor, Doina G. Andronoiu, Gabriel D.\nMocanu and Ioana O. Ghinea",downloadPdfUrl:"/chapter/pdf-download/55567",previewPdfUrl:"/chapter/pdf-preview/55567",authors:[{id:"150208",title:"Dr.",name:"Gabriel - Danut",surname:"Mocanu",slug:"gabriel-danut-mocanu",fullName:"Gabriel - Danut Mocanu"},{id:"150936",title:"Prof.",name:"Elisabeta",surname:"Botez",slug:"elisabeta-botez",fullName:"Elisabeta Botez"},{id:"177240",title:"Dr.",name:"Ioana Otilia",surname:"Ghinea",slug:"ioana-otilia-ghinea",fullName:"Ioana Otilia Ghinea"},{id:"202904",title:"Dr.",name:"Oana-Viorela",surname:"Nistor",slug:"oana-viorela-nistor",fullName:"Oana-Viorela Nistor"},{id:"202905",title:"Dr.",name:"Georgeta Doina",surname:"Andronoiu",slug:"georgeta-doina-andronoiu",fullName:"Georgeta Doina Andronoiu"}],corrections:null},{id:"55649",title:"Liposomes as Matrices to Hold Bioactive Compounds for Drinkable Foods: Their Ability to Improve Health and Future Prospects",doi:"10.5772/intechopen.69117",slug:"liposomes-as-matrices-to-hold-bioactive-compounds-for-drinkable-foods-their-ability-to-improve-healt",totalDownloads:1750,totalCrossrefCites:4,totalDimensionsCites:4,hasAltmetrics:1,abstract:"The aim of this chapter is to describe the use of bioactive compounds with beneficial effects on human health beyond their basic nutritional value. Bioactive compounds like vitamin E, vitamin C, and fatty acids (omega-3 and omega-6) have an important nutritional contribution and are related to the prevention of certain diseases with global impact such as cancer. However, the addition of vitamins in a food product is not easy: E is destroyed by UV-light, and C is dramatically reduced during heat processes. The use of liposomes as matrices to hold bioactive compounds appears to be a promising solution. Liposomes were made of natural soybean lecithin, which has a great nutritional importance, and more so combined with stearic acid or calcium stearate (CaS). Thus, this stabilize liposomes and contribute to the stability of bioactive compounds and to preserve their activity. The stability of bioactive compounds/liposomes incorporated into aqueous food must be demonstrated in properties such as oxidative tendency, morphology, size, and membrane packaging after heat treatment processes. But to make a product applicable at the commercial level, its texture and mouthfeel arising from the ingestion of drinkable foods are all-important to consumer’s choice and sensory acceptability must not undergo any modification.",signatures:"Marina Marsanasco, Nadia Silvia Chiaramoni and Silvia del Valle\nAlonso",downloadPdfUrl:"/chapter/pdf-download/55649",previewPdfUrl:"/chapter/pdf-preview/55649",authors:[{id:"203036",title:"Dr.",name:"Silvia Del Valle",surname:"Alonso",slug:"silvia-del-valle-alonso",fullName:"Silvia Del Valle Alonso"},{id:"203038",title:"Prof.",name:"Marina",surname:"Marsanasco",slug:"marina-marsanasco",fullName:"Marina Marsanasco"},{id:"203039",title:"Dr.",name:"Nadia S.",surname:"Chiaramoni",slug:"nadia-s.-chiaramoni",fullName:"Nadia S. Chiaramoni"}],corrections:null},{id:"55573",title:"Food Metabolomics: A New Frontier in Food Analysis and its Application to Understanding Fermented Foods",doi:"10.5772/intechopen.69171",slug:"food-metabolomics-a-new-frontier-in-food-analysis-and-its-application-to-understanding-fermented-foo",totalDownloads:2218,totalCrossrefCites:9,totalDimensionsCites:16,hasAltmetrics:0,abstract:"The emergence of food metabolomics, otherwise known as foodomics, has opened new frontiers and possibilities for scientists to characterize and simultaneously determine and obtain the comprehensive profile of the food metabolome. Qualitative and quantitative determinations of this metabolome offer insights into the underlying processes involved and details about the content of the food analytes. This had seemed technically challenging and impossible over time, but can now be done due to the advent of sophisticated analytical equipment and chemometric tools. The application of this technique offers enormous opportunities to obtain detailed information that can be correlated to various properties, functionalities and potentials in fermented foods. This chapter thus evaluated and documented studies presented in the literature on the food metabolomics study of fermented foods, with a view of appraising its prospects, applications and subsequent utilization in the study of fermented foods.",signatures:"Oluwafemi Ayodeji Adebo, Patrick Berka Njobeh, Janet Adeyinka\nAdebiyi, Sefater Gbashi and Eugenie Kayitesi",downloadPdfUrl:"/chapter/pdf-download/55573",previewPdfUrl:"/chapter/pdf-preview/55573",authors:[{id:"60387",title:"Prof.",name:"Patrick Berka",surname:"Njobeh",slug:"patrick-berka-njobeh",fullName:"Patrick Berka Njobeh"},{id:"201370",title:"Dr.",name:"Oluwafemi",surname:"Adebo",slug:"oluwafemi-adebo",fullName:"Oluwafemi Adebo"},{id:"201371",title:"Dr.",name:"Eugenie",surname:"Kayitesi",slug:"eugenie-kayitesi",fullName:"Eugenie Kayitesi"},{id:"201372",title:"MSc.",name:"Janet",surname:"Adebiyi",slug:"janet-adebiyi",fullName:"Janet Adebiyi"},{id:"201373",title:"Dr.",name:"Sefater",surname:"Gbashi",slug:"sefater-gbashi",fullName:"Sefater Gbashi"}],corrections:null},{id:"55684",title:"Models to Evaluate the Prebiotic Potential of Foods",doi:"10.5772/intechopen.69174",slug:"models-to-evaluate-the-prebiotic-potential-of-foods",totalDownloads:2265,totalCrossrefCites:5,totalDimensionsCites:9,hasAltmetrics:1,abstract:"The interest in studying the prebiotic effect of foods is increasing due to the way in which the consumption of these foods influences the gut microbiota and how the metabolic activity of the microbiota affects the health and well‐being of the host. Several in vitro and in vivo studies have been developed to elucidate the prebiotic effect of foods, and particularly in in vivo studies, the physiological dynamics of this effect has been studied in healthy or diseased individuals. In this chapter, the main in vitro and in vivo models developed for the study of the prebiotic potential of foods will be approached, which can be used by those planning to advance in this field of research.",signatures:"Jailane de Souza Aquino, Kamila Sabino Batista, Francisca Nayara\nDantas Duarte Menezes, Priscilla Paulo Lins, Jessyca Alencar de\nSousa Gomes and Laiane Alves da Silva",downloadPdfUrl:"/chapter/pdf-download/55684",previewPdfUrl:"/chapter/pdf-preview/55684",authors:[{id:"200932",title:"Ph.D.",name:"Jailane",surname:"De Souza Aquino",slug:"jailane-de-souza-aquino",fullName:"Jailane De Souza Aquino"},{id:"202942",title:"MSc.",name:"Francisca Nayara",surname:"Menezes",slug:"francisca-nayara-menezes",fullName:"Francisca Nayara Menezes"},{id:"202943",title:"Ph.D. Student",name:"Kamila",surname:"Batista",slug:"kamila-batista",fullName:"Kamila Batista"},{id:"202944",title:"Ms.",name:"Priscilla",surname:"Lins",slug:"priscilla-lins",fullName:"Priscilla Lins"},{id:"202945",title:"Ms.",name:"Jessyca",surname:"Gomes",slug:"jessyca-gomes",fullName:"Jessyca Gomes"},{id:"202946",title:"Ms.",name:"Laiane",surname:"Da Silva",slug:"laiane-da-silva",fullName:"Laiane Da Silva"}],corrections:null},{id:"56204",title:"Leveraging Bioactives to Support Human Health through the Lifecycle: Scientific Evidence and Regulatory Considerations",doi:"10.5772/intechopen.69836",slug:"leveraging-bioactives-to-support-human-health-through-the-lifecycle-scientific-evidence-and-regulato",totalDownloads:1505,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The identification of bioactive food components and understanding their role as adjunct therapeutic agents in disease management and prevention has become a significant area of research. Accumulating evidence suggests a link between certain bioactive food components and health outcomes, for example, lutein and zeaxanthin for visual performance and delaying age-related macular degeneration, probiotics for gastrointestinal outcomes related to irritable bowel syndrome or prebiotics for its potential programming of the microbiome in early life to influence later life outcomes.. This rapidly developing science has triggered discussions to determine if public health recommendations can be made on bioactive foods. However, regulatory guidance is necessary to guide the development the science, it’s consideration for public health policy and the communication thereof to both healthcare professionals and consumers. This chapter will focus on the clinical and basic science supporting a role for lutein and pre- and probiotics in modulating several aspects of human health, including the gut microbiome through the human lifecycle. Opportunities to translate the science to consumers in a meaningful and accurate way will also be highlighted along with the regulatory landscape to shape the testing, communication and commercialization of these bioactives.",signatures:"Deshanie Rai and Gyan Rai",downloadPdfUrl:"/chapter/pdf-download/56204",previewPdfUrl:"/chapter/pdf-preview/56204",authors:[{id:"201953",title:"Dr.",name:"Deshanie",surname:"Rai",slug:"deshanie-rai",fullName:"Deshanie Rai"},{id:"202095",title:"Dr.",name:"Gyan",surname:"Rai",slug:"gyan-rai",fullName:"Gyan Rai"}],corrections:null},{id:"56224",title:"Diet Quality Indices for Nutrition Assessment: Types and Applications",doi:"10.5772/intechopen.69807",slug:"diet-quality-indices-for-nutrition-assessment-types-and-applications",totalDownloads:4557,totalCrossrefCites:4,totalDimensionsCites:13,hasAltmetrics:0,abstract:"According to the World Health Organization, the proportion of noncommunicable diseases (NCD) burden is foreseen to increase to 57% in 2020. Consumption patterns have a positive effect on healthy growth and development during childhood and adolescence, and on health problems in adulthood. Diet quality indices are mathematical algorithms used for nutritional epidemiology, aimed at quantifying the degree of adequacy between actual intakes of nutrients or food groups within a population and the reference intakes, which are established based on scientific facts assuring an optimal state of health while preventing consumers from chronic diseases. Similarly, indexes allow to analyse dietary pattern of target population and its consumption trends. In general the terms, DQI (Diet Quality Index), HDI (Healthy Diet Indicator) and MDS (Mediterranean Diet Score), are referred to three internationally recognized diet indexes, which several indices have been adapted from. This chapter includes an extensive review of existing diet indexes, 1) providing a brief description of the most relevant ones, 2) highlighting the weaknesses and strengths and 3) defining the suitable scope of application of each index.",signatures:"Maria Luisa Poyatos Guerrero and Fernando Pérez-Rodríguez",downloadPdfUrl:"/chapter/pdf-download/56224",previewPdfUrl:"/chapter/pdf-preview/56224",authors:[{id:"82252",title:"Dr.",name:"Fernando",surname:"Pérez-Rodríguez",slug:"fernando-perez-rodriguez",fullName:"Fernando Pérez-Rodríguez"},{id:"207713",title:"MSc.",name:"Maria Luisa",surname:"Poyatos-Guerrero",slug:"maria-luisa-poyatos-guerrero",fullName:"Maria Luisa Poyatos-Guerrero"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8311",title:"Nutraceuticals",subtitle:"Past, Present and 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Kim",dateSubmitted:"February 17th 2020",dateReviewed:"April 16th 2020",datePrePublished:"June 15th 2020",datePublished:"April 14th 2021",book:{id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",fullTitle:"Satellite Systems - Design, Modeling, Simulation and Analysis",slug:"satellite-systems-design-modeling-simulation-and-analysis",publishedDate:"April 14th 2021",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"316140",title:"Dr.",name:"Yuri",middleName:null,surname:"Kim",fullName:"Yuri Kim",slug:"yuri-kim",email:"yurikim@hotmail.ca",position:null,institution:{name:"Canadian Space Agency",institutionURL:null,country:{name:"Canada"}}}]}},chapter:{id:"72485",slug:"satellite-control-system-part-i-architecture-and-main-components",signatures:"Yuri V. Kim",dateSubmitted:"February 17th 2020",dateReviewed:"April 16th 2020",datePrePublished:"June 15th 2020",datePublished:"April 14th 2021",book:{id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",fullTitle:"Satellite Systems - Design, Modeling, Simulation and Analysis",slug:"satellite-systems-design-modeling-simulation-and-analysis",publishedDate:"April 14th 2021",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"316140",title:"Dr.",name:"Yuri",middleName:null,surname:"Kim",fullName:"Yuri Kim",slug:"yuri-kim",email:"yurikim@hotmail.ca",position:null,institution:{name:"Canadian Space Agency",institutionURL:null,country:{name:"Canada"}}}]},book:{id:"7030",title:"Satellite Systems",subtitle:"Design, Modeling, Simulation and Analysis",fullTitle:"Satellite Systems - Design, Modeling, Simulation and Analysis",slug:"satellite-systems-design-modeling-simulation-and-analysis",publishedDate:"April 14th 2021",bookSignature:"Tien Nguyen",coverURL:"https://cdn.intechopen.com/books/images_new/7030.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"210657",title:"Dr.",name:"Tien M.",middleName:"Manh",surname:"Nguyen",slug:"tien-m.-nguyen",fullName:"Tien M. Nguyen"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"2406",leadTitle:null,title:"Landscape Planning",subtitle:null,reviewType:"peer-reviewed",abstract:"Landscape architecture is the design of outdoor and public spaces to achieve environmental, socio-behavioral, and/or aesthetic outcomes. It involves the systematic investigation of existing social, ecological, and geological conditions and processes in the landscape, and the design of interventions that will produce the desired outcome. The scope of the profession includes: urban design; site planning; town or urban planning; environmental restoration; parks and recreation planning; visual resource management; green infrastructure planning and provision; and private estate and residence landscape master planning and design - all at varying scales of design, planning and management. This book contains chapters on recent developments in studies of landscape architecture. For this reason I believe the book would be useful to the relevant professional disciplines.",isbn:null,printIsbn:"978-953-51-0654-8",pdfIsbn:"978-953-51-5304-7",doi:"10.5772/2761",price:139,priceEur:155,priceUsd:179,slug:"landscape-planning",numberOfPages:374,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"3c7b088d1bfbcf17d7f2fe6f47137af2",bookSignature:"Murat Ozyavuz",publishedDate:"June 13th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2406.jpg",keywords:null,numberOfDownloads:67009,numberOfWosCitations:50,numberOfCrossrefCitations:19,numberOfDimensionsCitations:67,numberOfTotalCitations:136,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 25th 2011",dateEndSecondStepPublish:"November 18th 2011",dateEndThirdStepPublish:"January 27th 2012",dateEndFourthStepPublish:"February 26th 2012",dateEndFifthStepPublish:"April 26th 2012",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"11 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"93073",title:"Dr.",name:"Murat",middleName:null,surname:"Ozyavuz",slug:"murat-ozyavuz",fullName:"Murat Ozyavuz",profilePictureURL:"https://mts.intechopen.com/storage/users/93073/images/549_n.jpg",biography:"Assoc. Prof. Dr. Murat Ozyavuz was born in 1976 in Turkey and lived there until coming to Ankara (Turkey) in 1999. He studied Landscape Architecture at the Ankara University and obtained B.S. degree in 1999. He obtained his M.S. and Ph.D. degrees from the Landscape Architecture Department of Institute of Natural and Applied Sciences in 2003 and July 2008, respectively (M. S. Thesis, Arboretum Planning Principles and Thrace University Güllapoğlu Arboretum Landscape Planning Studies, Ph.D. thesis, Planning of İğneada – Demirköy Part of Yildiz Mountains as a Biosphere Reserve). During his Ph.D. studies, he mostly worked on Landscape Planning, Protected Areas, Geographic Information Systems and Remote Sensing. Now, Dr. Ozyavuz is an Associate Professor at the Department of Landscape Architecture, Faculty of Fine Arts, Design and Architect, Namık Kemal University. He has many national and international publications and has worked on many research projects.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Namık Kemal University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"849",title:"Landscape Ecology",slug:"landscape-ecology"}],chapters:[{id:"37552",title:"Protected Areas",slug:"protected-areas",totalDownloads:2227,totalCrossrefCites:0,authors:[{id:"93073",title:"Dr.",name:"Murat",surname:"Ozyavuz",slug:"murat-ozyavuz",fullName:"Murat Ozyavuz"}]},{id:"37553",title:"Land Use/Cover Classification Techniques Using Optical Remotely Sensed Data in Landscape Planning",slug:"land-use-cover-classification-techniques-using-optical-remotely-sensed-data-in-landscape-plannin",totalDownloads:5502,totalCrossrefCites:1,authors:[{id:"128217",title:"Dr.",name:"Onur",surname:"Satir",slug:"onur-satir",fullName:"Onur Satir"},{id:"138523",title:"Prof.",name:"Suha",surname:"Berberoglu",slug:"suha-berberoglu",fullName:"Suha Berberoglu"}]},{id:"37554",title:"GIS in Landscape Planning",slug:"gis-in-landscape-planning",totalDownloads:5777,totalCrossrefCites:2,authors:[{id:"127480",title:"Prof.",name:"Matthias",surname:"Pietsch",slug:"matthias-pietsch",fullName:"Matthias Pietsch"}]},{id:"37555",title:"An Approach to Landscape Planning in Borders",slug:"landscape-planning-in-borders",totalDownloads:3505,totalCrossrefCites:1,authors:[{id:"136991",title:"MA",name:"Gloria",surname:"Aponte",slug:"gloria-aponte",fullName:"Gloria Aponte"}]},{id:"37556",title:"Urban Green Space System 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by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"56959",title:"Low Melting Temperature Solder Materials for Use in Flexible Microelectronic Packaging Applications",doi:"10.5772/intechopen.70272",slug:"low-melting-temperature-solder-materials-for-use-in-flexible-microelectronic-packaging-applications",body:'\nMore advanced solder bumps with low melting temperatures are crucial for use in flexible, bendable, and stretchable interconnection technology [1, 2]. In particular, the use of wearable devices requires the development of novel solders that can be reflowed at low temperature to avoid thermal damage to the usually temperature-sensitive components in these flexible devices, such as organic light-emitting diodes (OLEDs), polymer light-emitting diodes (PLEDs), and so on [3–6]. Thus, it is worthwhile to design a low melting temperature solder for more advanced interconnection technology and thus to impart more reliability to the solder bumps between future organic- or polymer-based microchips and flexible substrates. Furthermore, the continuous pursuit of multifunctionality in microelectronics has caused a significant increase in the number of solder bumps, to the level of 10,000 per chip [7]. It also has decreased the bump size to as small as 20 μm [7]. Thus, solder bumps with enhanced electrical and thermomechanical properties are needed to meet these demands. With these uses in mind, the properties of conventional solder materials with high melting temperatures (180–230°C) have been under scrutiny due to their reference characteristics, and whether implementing currently used soldering methods or inventing new ones, solution strategies to overcome problems associated with novel solder materials have been implemented.
\nIn this chapter, we focus on the electrical and thermo-mechanical properties of novel solder materials with a specific range of low melting temperatures (<150°C). Emerging carbon reinforcement materials, such as carbon nanotubes (CNTs), graphenes, and their nanocomposites, are also briefly discussed and linked to the increasing development of composite solder materials (in addition to their low melting temperatures). In particular, strategies for improving the performance of solder materials are proposed, along with the provision of insight into classic metallurgy principles. To engineer the properties of low melting temperature solder materials in intended directions, new approaches using nanostructures, nanocomposites, alloying, and doping are also suggested.
\nIn this section, we show how low melting temperature solders, consisting of various elements with higher melting temperatures, such as Sn (melting point of 231.9°C), In (melting point of 156.6°C), and Bi (melting point of 271.5°C), can be fabricated and/or synthesized using metallurgy principles or nanotechnology theory [8]. For example, the formation of an eutectic alloy with 42 wt.% Sn and 58 wt.% Bi can lead to a melting point decrease to 138°C due to the shift to the eutectic temperature [3, 4]. Due to the melting point drop according to the size decrease, the size reduction effect can also be used to synthesize a low melting point solder [4].
\nLow melting temperature Sn–In solder nanoparticles were successfully synthesized through a surfactant-assisted one-step chemical reduction method [9]. Different synthesis parameters, including pH, stirring speed, and surfactant concentration, were used to control the size, shape, and uniformity of the Sn–In solder nanoparticles [9]. At low In composition (20 wt.% In), the Sn–In solder nanoparticles were composed of InSn4 alloy and β-Sn phase [9]. When the In content increased to 30 wt.%, the Sn–In solder nanoparticles were composed mainly of InSn4, with a melting temperature of 115.5°C [9]. This low melting temperature indicates a new eutectic point for the Sn–In solder nanoparticle system, which is lower than that of the bulk alloy system (around 50 wt.% In) [9]. At higher In compositions, the Sn–In solder nanoparticles are composed of both InSn4 and In phase [9].
\nTo increase the compatibility and usefulness of the low melting point solder, eutectic Bi–43Sn nanowires with diameters of 20, 70, and 220 nm were fabricated by a hydraulic pressure injection process using anodic aluminum oxide templates [10]. Their microstructure investigation showed that the fabricated nanowires are composed of alternating Bi and Sn segments along the wire axes [10].
\nNovel Sn–Bi nanocomposites reinforced with reduced graphene oxide nanosheets (RGONs) were successfully fabricated by a simple, scalable, and economical electrochemical deposition method [11]. The Sn–Bi nanocomposites, reinforced with reduced graphene oxide nanosheets, had fine grain size as well as reduced graphene oxide nanosheets dispersed throughout the Sn–Bi matrix [11].
\nFor the microstructural transformation and thermoelectrical improvement of Sn–Bi solder, MWCNT was reinforced using the electrochemical codeposition method [11]. Electron microscopy analysis can confirm that pristine MWCNTs were trapped in the deposited composites [11].
\nBi-based solder powders with three chemical compositions (binary Bi–Sn, ternary Bi–Sn–In, and quaternary Bi–Sn–In–Ga alloy systems) were fabricated using a gas atomization technique; subsequently, the powders were further ball-milled to fabricate smaller-sized particulates; in particular, the diameter of those in the Bi–Sn–In–Ga powders became less than 10 μm with an irregular shape due to the nature of intrinsic brittleness, the degree of surface oxidation, and the formation of Ga intermetallic compound (IMC), all of which produced fractures of the Ga-containing powders [3].
\nTernary Bi–Sn–In micropowders and nanoparticles were prepared as a composite solder material via gas atomization process and a chemical reduction method, respectively [3, 4]. To be specific, two types of Bi-based micropowders, composed of binary Bi–Sn and ternary Bi–Sn–In, were fabricated using a gas atomizer [4]. Then, the gas-atomized powders were classified using a series of standard sieves to obtain powders of a specific size range [4]. Bi (III) nitrate pentahydrate, Sn (II) 2-ethylhexanoate, In (III) nitrate hydrate at a Bi/Sn/In weight ratio of 43.5/31.5/25.0, and 1,10-phenanthroline were added to methanol, and the solution was stirred for 2 h [4]. Then, sodium borohydride was added, and the reaction continued at 50°C for 1 h [4]. The as-synthesized nanoparticles were centrifuged at 4000 rpm for 15 min, washed with methanol, and then dried in a vacuum oven for 24 h [4].
\nConventional, low melting temperature solders are fabricated using either Sn–Bi or Sn–In [12]. In particular, Sn–Bi solders have received considerable attention because of their outstanding merits, including high wetting behavior, large creep resistance, and low coefficient of thermal expansion [12–14]. However, the relatively low mechanical strength and melting temperature (138°C) of these materials require improvement for their more effective use in flexible interconnection applications [3, 15]. Comparatively, Sn–In solder, which has a low melting temperature (118 °C), has excellent electrical and thermal properties [12, 16]. However, the price of In is very high, and this material includes high amounts of IMCs, which degrade the mechanical properties of the solder [16]. Thus, the incorporation of additives, including alloying, doping, or the use of reinforcement materials, into Sn–Bi or Sn–In alloy systems has been considered a useful strategy for improving the mechanical properties.
\nThe microstructure reflects the mechanical properties of a solder [15–21]. Based on the microstructural analysis of low melting point solders, specific phases and their distribution in the microstructure can be observed, and these characteristics can be used to describe intended properties [15–21]. In this section, we show how the microstructure of low melting point solders is altered by the incorporation of an additive, especially with regard to grain size and solid solution.
\nThe representative microstructure of eutectic Sn–Bi alloy is shown in Figure 1; in this structure, granular Sn-rich grains and similarly granular Bi-rich grains can be seen. The dark and bright gray regions are Sn and Bi, respectively; these regions appear as interlocked lamellar structures. Upon incorporation of an additive into the Sn–Bi solder, the solder microstructure was found to be remarkably transformed due to the formation of finer grains or the presence of new solid solutions or precipitates. Usually, a plausible explanation for this is that Sn- and Bi-rich grains are heterogeneously nucleated in the formation of certain IMCs. For example, Mokhtari et al. demonstrated that the addition of In or Ni can modify the microstructure of Sn–Bi solder; in particular, the addition of 0.5 wt.% In was able to suppress the coarsening of the Bi-rich phase, which means that the Sn–Bi–0.5In solder comprised primary Sn dendrites and eutectic phases [13, 15]. Comparatively, Ni appears to have been included in the Sn phase since Ni-containing Sn–Bi solder exhibited eutectic phases and the Ni3Sn4 IMC but did not show any sign of coarsening due to the Bi-rich phase.
\nSEM micrographs of (a) eutectic Sn–Bi, (b) Sn–Bi–0.5In, and (c) Sn–Bi–0.5Ni [
Figure 2 exhibits the cross-sectional microstructure of a Sn–40Bi–2Zn–0.1Cu solder alloy composed of Sn-, Bi-, Zn-, and Cu-rich phases. For the cooling (solidification) process of the Sn–40Bi–2Zn–0.1Cu solder alloy from the liquid state, the following procedure took place: L (liquid) → L + primary Sn → primary Sn + eutectic (β-Sn + Bi-rich) + eutectic (β-Sn + Zn-rich) → primary Sn + secondary precipitated Bi + eutectic (β-Sn + secondary precipitated Bi + Bi-rich) + eutectic (β-Sn + Zn-rich). Different from the reference Sn–40Bi–0.1Cu solder alloy, Cu6Sn5 precipitates were not found in the Sn–40Bi–2Zn–0.1Cu solder because Cu reacts more strongly with Zn than Sn does; thus, all of the Cu was consumed in the formation of Cu–Zn IMCs [17]. These results were also very similar to the studies of Islam and Li [22, 23]. According to the X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) analysis, globular CuZn2 and blocky Cu5Zn8 precipitates were formed in Sn–40Bi–2Zn–0.1Cu solder; in particular, Zn atoms segregated between the Sn- and Bi-rich matrices and reacted with Cu atoms to form Cu–Zn IMC particles [17].
\nSEM micrograph and EDS analysis results of (a) Cu6Sn5 phase in Sn–40Bi–0.1Cu, (b) CuZn2 phase in Sn–40Bi–2Zn–0.1Cu, and (c) Cu5Zn8 phase in Sn–40Bi–2Zn–0.1Cu [
Figure 3 shows the microstructures of the Sn–58Bi and Sn–Bi–Sb alloys. The Sn–58Bi alloy shows a typical eutectic structure. The dark region is the Sn phase; the white region represents the Bi phase. For the Sn–Bi–Sb alloys, each part contains two phases, the dark and the light phases shown, respectively, in the images. When the Bi content changes, the proportion of each structure does not greatly change. However, the proportion of quasi-peritectic structure increases, as the Sb content increases [18]. For the Sn–Bi–Sb alloy, the intensity of the Sn-rich phases increased when the Sb content increased [18].
\nSEM micrographs of Sn–58Bi and Sn–Bi–Sb alloys: (a and d) Sn–58Bi, (b and e) Sn–52Bi–1.8Sb, (c and f) Sn–48Bi–1.8Sb, (g) Sn–48Bi–1.4Sb, (h) Sn–48Bi–1.8Sb, and (i) Sn–48Bi–2.4Sb [
The near eutectic solder (In–50Sn) is presented in Figure 4a, showing a cross-sectional microstructure consisting of a combination of lamellar and irregular phases. In particular, the presence of a mixture of Sn-rich and In-rich phases and the In3Sn IMC was determined by XRD and EDS analyses. Comparatively, Figure 4b shows the cross-sectional microstructure of the In–30Sn solder, which consisted of only two specific phases: an In-rich phase and the In3Sn IMC but the absence of Sn-rich phases and/or other Sn IMCs [16].
\nSEM micrographs of (a) In–50Sn and (b) In–30Sn solders [
As can be seen in Figure 5, the interfacial bonding of low melting temperature Sn–In solder on the Cu substrate is presented according to the reflow temperature and duration. The reflow at 180°C for 20 min selected was the optimal condition due to the high bonding strength of 6.5 MPa and the interfacial layer with less microvoids or mechanical cracks [20]. Especially, the reflow temperature of 180°C was high enough for the active diffusion of the low melting temperature solders, although they were dissolved in the Cu substrates and formed IMCs such as Cu6(Sn, In)5 and Cu11(In, Sn)9 [20]. Therefore, the joint can sustain high service temperatures because it is formed completely from these IMCs.
\nSEM micrographs (top) of as-received coating surface: (a) top view and (b) cross section. Cross-sectional SEM images (bottom) show that at the interfacial layers between the Sn-based solder and the cu substrate, the two components reacted and diffused under the following conditions (reflow temperature (°C) and duration (min)): (a) 140 and 5; (b) 140 and 20; (c) 160 and 5; (d) 160 and 20; (e) 180 and 5; and (f) 180 and 20 [
Chen et al. determined the interfacial reactions in Sn–51In, Sn–20In, and Sn–20In–2.8Ag on Ag substrates reacted at various temperatures, with results shown in Figure 6 [21]. Particularly for the Sn–51In/Ag couples, the reaction products are AgIn2 and Ag2In phases at 150°C and 100°C; only Ag2In is formed at lower temperatures [21]. Due to the formation of different reaction phases, the reaction layer in the Sn–51In/Ag couples grows more slowly at 100°C than is the case for samples reacted at lower temperatures [21]. The interfacial reaction rates in the Sn–20In/Ag couples are much slower than those in the Sn–51In/Ag couples [21]. In the Sn–20In/Ag couples, the ζ-phase is formed at 250°C, and both ζ-Ag/AgIn2 phases are formed at 125°C; however, no noticeable interfacial reactions are observed to have reacted at 75 and 100°C over a period of 1440 h [21].
\nBackscattered electron imaging (BEI) micrographs (top) of (a) Sn–1.98 at.% In–8.03 at.% Ag, (b) Sn–10.02 at.% In–10.01 at.% Ag, (c) Sn–16.99 at.% In–80.01 at.% Ag, and (d) Sn–29.99 at.% In–68.99 at.% Ag annealed at 250°C for 12 weeks. BEI micrographs (bottom) of Sn–51In/Ag couple reacted at (a) 75°C, (b) 50°C, and (c) 25°C for 120 h [
The species of IMCs at the interface between the eutectic Sn–In solder and the single crystalline Cu substrate were systematically investigated using scanning electron microscopy (SEM) (Figure 7). After reflowing at 160°C for 5 s, two kinds of IMC were formed in three sublayers from the solder to the substrate side; the formed materials were a Cu(In, Sn)2 layer with tetragonal crystal structure, a coarse-grain Cu2(In, Sn) sublayer, and a fine-grain Cu2(In, Sn) sublayer with hexagonal crystal structure [24]. The morphology of the Cu(In, Sn)2 grains is chunk type, the largest grain size. In the process of increased liquid soldering, this Cu(In, Sn)2 layer is prone to spalling into the solder, leaving a duplex structure of Cu2(In, Sn) as the dominating IMC, which should be paid attention during phase identification [24]. The fine-grain Cu2(In, Sn) shows a granule-type morphology with the smallest grain size; this material distributes homogeneously on the entire Cu substrates [24]. However, coarse-grain Cu2(In, Sn) is substrate dependent and has an elongated morphology on single crystalline Cu surfaces [24].
\nCross-sectional SEM micrograph at the interface between eutectic Sn–In solder and single crystalline (1 1 1) Cu after reflowing at 160°C for 5 s [
The SEM micrographs (Figure 8) show Sn–58Bi solders doped with different weight fractions of graphene nanosheets (GNSs). In particular, Figure 8a shows the typical lamellar structure of the eutectic Sn–58Bi solder, in which the dark regions represent the Sn-rich phase, while the white regions represent the Bi-rich phase. Compared to the standard Sn–58Bi solder alloy, the microstructure of the composite solder is refined due to the increased content of graphene nanosheets, as shown in Figure 8b–e. The average grain size of the pure sample was about 1.6 μm, which is higher than that of the graphene nanosheet-doped solder samples [19]. The size reductions of the Sn–58Bi–graphene nanosheet (0.01, 0.03, 0.05, 0.1 wt.%) solders were about 28, 55, 30, and 32%, respectively [19]. These results indicate that the growth of grains was suppressed, and the microstructure of the Sn–58Bi solder alloys was refined by the addition of graphene nanosheets; in addition, the solder alloy with 0.03 wt.% graphene nanosheet addition showed the smallest average grain size [19]. The microstructure of local refinement can be found in Figure 8b for the 0.01 wt.% graphene nanosheet addition; meanwhile, uniform refinement of the structure and small Bi grains appear in the Sn–58Bi reinforced with 0.03 wt.% graphene nanosheets, shown in Figure 8c. These images indicate that the growth of grains can be suppressed by the presence of graphene nanosheets, which is caused by the high barrier of graphene nanosheets against the diffusion of metal atoms [19]. However, with more graphene nanosheets introduced, the growth of metal grains along the surface of the graphene nanosheets can be promoted [19]. As a result, the distinct feature of the uniformly distributed dendritic structure in Sn–58Bi reinforced with 0.05 wt.% graphene nanosheets can be seen in Figure 8d; this structure shows that graphene nanosheets can promote the growth of Bi dendrites. Moreover, local grain aggregation recurs and partial grains growth follows an inverse pattern when the content of graphene nanosheets reaches 0.1 wt.%, as shown in Figure 8e. This result is attributed to the increasing addition of graphene nanosheets, which undergo effective bonding with solders [19].
\nSEM micrographs of (a) Sn–58Bi, (b) Sn–58Bi–0.01GNSs, (c) Sn–58Bi–0.03GNSs, (d) Sn–58Bi–0.05GNSs, and (e) Sn–58Bi–0.1GNSs [
The solder bump size on a packaging substrate decreases as a result of the electronic components being miniaturized [25–28]. Simultaneously, the pitch distance drops to the submicron level [27, 28]. The pin count increases to meet the demands of rapid signal transmission and high current load [28]. Thus, the electrical property of a solder becomes one of the most important factors [29–31]. In the literature, however, there is not much research on the electrical properties of low melting point solders. Thus, determining the electrical property for a low melting point solder can be of great use to researchers and engineers, especially those who design solder alloys. Meanwhile, the eutectic Sn–Bi solder has a relatively high electrical resistivity of 30–35 μΩ·cm due to the electrical resistivity of Bi (115 μΩ·cm), while the eutectic Sn–In solder has a very low electrical resistivity of 10–15 μΩ·cm due to the electrical resistivity of In (8 μΩ·cm) [30].
\nAltıntas et al. determined that the electrical conductivity varies with temperature for low melting point solders: Sn–41.39 at.% Cd–6.69 at.% Sb, Sn–49 at.% In–1 at.% Cu, Sn–50 at.% Ag–10 at.% Bi, and Sn–32 at.% Bi–3 at.% Zn alloys; these values were determined by the four-point probe method, as shown in Figure 9 [31]. The electrical conductivities of all solder alloys in the present work were found to decrease linearly with increasing temperature. The electrical conductivity values as a function of temperature were found to be in ranges of 4.35–2.76, 5.00–3.43, 5.30–4.58, and 1.52–1.39 (× 106)/Ω·m for Sn–Cd–Sb, Sn–In–Cu, Sn–Ag–Bi, and Sn–Bi–Zn solder alloys, respectively [31]. By extrapolating the electrical conductivity lines to their melting temperature, values of electrical conductivity for Sn–Cd–Sb, Sn–In–Cu, Sn–Ag–Bi, and Sn–Bi–Zn at their melting temperatures were determined to be 2.61, 3.26, 4.57, and 1.35 (× 106)/Ω·m, respectively, as shown in Table 1.
\nElectrical conductivity measurements according to temperature for (a) Sn–41.39Cd–6.69Sb, (b) Sn–49In–1Cu, (c) Sn–50Ag–10Bi, and (d) Sn–32Bi–3Zn (at.%) solder alloys [
\n | Melting temperature (K) | \nTemperature coefficient of σ (K−1) × 10−3 | \nσ at the melting temp (1/Ω·m) × 106 | \n
---|---|---|---|
Sn–41.39 at.% Cd–6.69 at.% Sb | \n453 | \n2.47 | \n2.61 | \n
Sn–49 at.% In–1 at.% Cu | \n389 | \n4.97 | \n3.26 | \n
Sn–50 at.% Ag–10 at.% Bi | \n411.4 | \n1.14 | \n4.57 | \n
Sn–32 at.% Bi–3 at.% Zn | \n404.7 | \n1.00 | \n1.35 | \n
Sn–4 wt.% Ag–2 wt.% In | \n490.7 | \n– | \n– | \n
Sn–20 wt.% Ag–2 wt.% In | \n490.7 | \n– | \n– | \n
Sn–40 wt.% Ag–2 wt.% In | \n490.7 | \n– | \n– | \n
Sn–20 wt.% In–25 wt.% Ag | \n490.7 | \n– | \n– | \n
Sn–20 wt.% In–10 wt.% Ag | \n490.7 | \n– | \n– | \n
Sn–20 wt.% In–15 wt.% Ag | \n486.0 | \n– | \n– | \n
Sn–6 wt.% Sb–5 wt.% Ag | \n507.8 | \n– | \n– | \n
Sn–42.8 wt.% Bi–0.04 wt.% Cu | \n411.8 | \n– | \n– | \n
Sn–3.5 wt.% Ag–0.9 wt.% Cu | \n490.2 | \n– | \n– | \n
Some electrical properties of solid phase for Sn–41.39 at.% Cd–6.69 at.% Sb, Sn–49 at.% In–1 at.% Cu, Sn–50 at.% Ag–10 at.% Bi, Sn–32 at.% Bi–3 at.% Zn [31].
Figure 10 depicts the resistivity of all Sn–Bi solder alloys according to the increase of the Ni amount. No significant change in the electrical resistivity was detected following the addition of Ni. Although the existence of IMCs in the solders could induce a higher electrical resistivity, in this research the effect on the solders’ electrical resistivity in the presence of Ni3Sn4 is not apparent [29].
\nElectrical resistivity of Sn–58Bi–xNi [
The incorporation of carbon nanomaterials with graphene structures can also impart much more rapid electron transfer than that can be obtained using conventional Sn–Bi solder [32]. Subsequently, reinforcement with carbon nanomaterials having high thermal conductivity can be used to tailor a network structure to effectively transfer the outer thermal energy to the solder matrix [32]. Figure 11 shows the calculated current efficiency versus different MWCNT additions in the solder alloy. This implies that the current efficiency is dependent on the concentration of the solder constituent electrolytes [32]. This is mainly due to the increased hydrogen evolution caused by lower ion concentration in the vicinity of the nucleation/deposition sites [32]. On the other hand, the addition of MWCNTs into the solder alloy reduces the current efficiency because pristine MWCNTs are trapped in the deposited composites [32]. Due to the bridging effects of trapped MWCNTs, the Sn–Bi–CNT composite is denser than the pure Sn–Bi alloy [32].
\nCurrent efficiency change of the Sn–Bi solder under CNT load [
Near-future generations of electronics are expected to be flexible, bendable, and wearable [1]. The use of flexible devices requires the development of a novel solder that can be reflowed at a low temperature to avoid thermal damage to these flexible devices, which usually have temperature-sensitive components [3, 4]. In addition, the melting point of a solder alloy should be the first priority for consideration when it comes to the manufacturing process [3, 4]. Meanwhile, the eutectic point (usually, the low melting point) in a binary phase diagram is where a liquid phase and two solid phases can coexist at equilibrium. Thus, a large number of low melting point solders with eutectic compositions are mostly used for flip chip solder joint applications between microchips and substrates.
\nFigure 12 shows the solidus and liquidus temperatures, and the differences between both temperatures, referred to as the melting range of Sn–58Bi–xNi (x = 0.05, 0.1, 0.5 and 1.0 wt.%) solder alloys. The addition of Ni apparently lowered the solidus and liquidus temperatures [29]. This phenomenon was attributable to the fact that the addition of small amounts of Ni altered the composition of the alloy to resemble the eutectic composition of the ternary Sn–Bi–Ni alloy system [29].
\nSolidus and liquidus temperatures of Sn–58Bi–xNi [
Using the differential scanning calorimetry (DSC), when the content of In was increased to 23.8 wt.%. Kim et al. determined that the prominent endothermic peak of the Bi–Sn–In powders shifted to 82.0°C from that of the Bi–Sn powders, which have a peak at 139.6°C [3, 4]. The continuous addition of 4.8 wt.% Ga shifted the peak even more to 60.3°C. Meanwhile, there was a slight broadening in the solidus line of the melting peak of the Bi–Sn–In solder powders mainly due to the formation of an In-rich phase [3]. Furthermore, the formation of new Ga0.9In0.1, BiIn, and In0.2Sn0.8 IMCs according to the addition of 4.8 wt.% Ga to the Bi–Sn–In solder alloy system also influenced the melting range broadening [3]. Kim et al. also show that ternary Bi–Sn–In nanoparticles, with a 71.1°C melting temperature, entered among the intervals of the higher melting temperature (79.4°C) micropowders and then reflowed at 110°C on a flexible polyethylene terephthalate (PET) substrate [4].
\nThe fundamental thermal properties of Sn–58Bi–xZn (x = 0 and 0.7 wt.%) solder alloys were also analyzed by DSC, with results as shown in Figure 13. The results indicate that the solidus temperature of solder alloys slightly decreased with the addition of Zn content [33]. The reduction in solidus temperature of solders can probably be attributed to the increase in the surface instability due to the higher surface energy induced by the addition of Zn [33].
\nDSC curves of Sn–58Bi–xZn (x = 0 and 0.7) solders [
As can be seen in Figure 14a, the eutectic solder (In–Sn) had a low melting point of 118.5°C and a narrow melting range. The DSC curves of the hypo-eutectic Sn–70In and eutectic Sn–Bi solders were also presented in Figure 14b and c, respectively. In addition, the Bi53–Sn26–Cd21 solder presented in Figure 14d had the lowest melting temperature and a narrow melting range; thus, this solder had more active phase transformation than the others. The solidus temperatures, liquidus temperatures, and mushy temperature zones of Sn–58Bi, Sn–40Bi–0.1Cu, and Sn–40Bi–2Zn–0.1Cu solder alloys are collected in Table 2. The melting peak of the eutectic Sn–Bi solder decreased from 139.0 to 132.2°C according to the addition of a small amount of Cu; however, the addition of 2 wt.% Zn into the Cu-containing solder imparted a slight increase in the melting point (136.3°C) of the Sn–40Bi–2Zn–0.1Cu solder [17]. Thus, the addition of Cu decreased the melting point of the Sn–Bi-based solder, while the addition of Zn provided the reverse effect (melting temperature increase) [17]. Moreover, Cu addition decreased the melting range of the Sn–Bi-based solder from 27.2 to 22.0°C, while the addition of Zn to Sn–40Bi–2Zn–0.1Cu increased the melting range slightly to 23.1°C [17]. The thermal conductivity of the Sn–40Bi–2Zn–0.1Cu solder of 24.51 W/(m·K) was the highest, while the Sn–40Bi–0.1Cu solder took second place with a value of 20.48 W/(m·K). Zn and Cu additions obviously improved the thermal conductivity of the Sn–Bi-based solder alloy [17]. Aksoz et al. reported that the thermal conductivity of pure Zn is 116 W/(m·K), which is higher than those of pure Bi (8 W/(m·K)) and pure Sn (67 W/(m·K)) [34]. This is the reason that the Sn–40Bi–2Zn–0.1Cu solder has the highest thermal conductivity [34]. The temperatures of the endothermic peaks of the nine Sn–Bi–Sb alloys are shown in Table 3. All the main peaks appear at around 147°C. The melting range of all the Sn–Bi–Sb alloys is larger than that of the eutectic alloy [18]. Side peaks are observed in many DSC profiles of the Sn–Bi–Sb alloys [18]. As the Bi content is reduced, the melting range obviously becomes large. Meanwhile, the melting range and the liquidus temperature reached maximum values for the composition of Sn–48Bi–1.8Sb and then started to drop when Sb content changed [18]. The melting range may be attributed to the fact that the proportion of the eutectic structure will change when Bi or Sb content changes [18]. For the liquidus temperature, it was found that the primary phase changes to the β-Sn phase, when the Sb content is more than 1.8% [18]. The presence of second phase implies that the remaining primary phase continues to melt after quasi-peritectic reaction [18].
\nDSC curves of (a) In–50Sn, (b) In–30Sn, (c) Bi–42Sn, and (d) Bi–26Sn–21Cd solders [
Composition (wt.%) | \nSolid temperature (°C) | \nLiquid temperature (°C) | \nPasty range (°C) | \nMean TC (W/(mK)) | \n
---|---|---|---|---|
Sn-58Bi | \n130.2 | \n157.4 | \n27.2 | \n17.43 ± 0.6 | \n
Sn-40Bi-0.1Cu | \n125.1 | \n147.1 | \n22 | \n20.48 ± 0.3 | \n
Sn-40Bi-2Zn-0.1Cu | \n127.7 | \n150.8 | \n23.1 | \n24.51 ± 0.8 | \n
Solidus temperatures, liquids temperatures, melting ranges, and mean thermal conductivity of the solder alloys [17].
Composition (wt.%) | \nMain peak temperature (°C) | \nSec peak temperature (°C) | \nSolid temperature (°C) | \nLiquid temperature (°C) | \nMelting range (°C) | \n
---|---|---|---|---|---|
Sn–58Bi | \n143.1 | \n\n | 139.4 | \n148.0 | \n8.6 | \n
Sn–52Bi–1.8Sb | \n147.7 | \n\n | 140.6 | \n152.0 | \n11.4 | \n
Sn–48Bi–1.8Sb | \n146.5 | \n163.0 | \n140.9 | \n172.7 | \n31.8 | \n
Sn–44Bi–1.8Sb | \n146.9 | \n169.0 | \n141.9 | \n180.5 | \n38.6 | \n
Sn–48Bi–1.0Sb | \n144.7 | \n162.0 | \n140.6 | \n168.7 | \n28.1 | \n
Sn–48Bi–1.4Sb | \n146.8 | \n163.3 | \n141.2 | \n170.4 | \n29.2 | \n
Sn–48Bi–1.8Sb | \n146.5 | \n163.0 | \n140.9 | \n172.7 | \n31.8 | \n
Sn–48Bi–2.0Sb | \n147.6 | \n164.4 | \n142.3 | \n169.7 | \n27.4 | \n
Sn–48Bi–2.4Sb | \n148.5 | \n163.3 | \n142.8 | \n169.3 | \n26.5 | \n
Sn–48Bi–2.8Sb | \n148.0 | \n162.6 | \n143.6 | \n168.4 | \n24.8 | \n
Thermal behaviors of standard Sn–58Bi alloy, Sn–52Bi–1.8Sb alloys, and Sn–48Bi–xSn alloys [18].
Figure 15 shows the variation of the melting point of composite solder alloys with different dopant contents (both CNTs and Ni–CNTs) compared to the melting point of the Sn–57.6Bi–0.4Ag solder (about 140°C). It can be found that all the melting points were within the range of 139.3–139.6°C [35]. It has been reported that both CNTs and Ni–CNTs have an effect of reducing the melting point of solder alloys [35]. In particular, with the combined effect of CNTs and Ni–CNTs doped Sn–57.6Bi–0.4Ag solder alloys showed relatively lower melting points than those of CNTs doped solder alloys [35]. However, such small additions of CNTs and Ni–CNTs cannot have a significant influence on the melting point of Sn–57.6Bi–0.4Ag solder alloy [35].
\nPlot of the variation of melting point of solder alloys with different amounts of CNTs or NI–CNTs [
Figure 16 shows the DSC endothermic peaks of Sn–Bi nanocomposites reinforced with 0.02 or 0.05 g of reduced graphene nanosheets. While a large endothermic peak corresponding to the melting reaction in the range of 139.0°C of Sn–Bi solder has been observed, it was found that the melting point of Sn–Bi nanocomposites reinforced with reduced graphene nanosheets was about 139.0°C, which indicates that there was no significant effect on the thermal behavior of the nanocomposite solder, despite of the addition of reduced graphene nanosheets [11].
\nDSC of Sn–bi/RGOS nanocomposites with Sn content of 36.0 wt.% [
The durability and reliability of electronic products, as related to the mechanical properties of the solder joints, have become very important [13, 36–41]. This is especially true for portable, wearable devices, which frequently experience mechanical shock loadings caused by external forces [4]. Particularly for drop tests, during which the strain rate is very high, high mechanical shock resistance of solders is needed for these materials to fulfill their roles of structural materials. In addition, low melting point solders experience significantly high stresses during the reflow process owing to thermal gradient difference [3, 4]. Thus, there has been continuous interest in better understanding of the mechanical properties and in inventing high durability and reliability low melting point solders. One frequently utilized way to influence the mechanical properties of low melting point solder joints in a given system is to either alloy the materials or add small or large amounts of additional elements. In particular, any metal oxides or impurities may have marked effects on the mechanical properties of low melting point solders. Additional elements can fundamentally influence the mechanical properties of low melting point solders. First, additional elements can have an influence on the mechanical properties of the interfacial reactions between the solder and the substrate. Second, additives can positively change the mechanical properties of low melting point solders. Third, they can impart negative side effects, which result in a sacrifice of other mechanical properties of low melting point solders. In this section, therefore, we report on a number of investigations about the effects of different alloying elements, as well as the effects of metal oxides or impurities, in low melting point solders.
\nAfter the addition of 0.05 wt.% Cu6Sn5 nanoparticles in Sn–Bi solder, the tensile properties of the solder underwent brittleness caused by a change in ductility [36]. However, nanoindentation testing revealed that the creep resistance of the Sn–Bi–Cu6Sn5 solder is enhanced through the creep mechanism transformation [36]. In corrosion experiments, samples with Cu6Sn5 nanoparticles exhibit a lower corrosion rate [36].
\nAdding different sized Ag nanoparticles to a eutectic Sn–Bi alloy system refined the grain (microstructure), suppressed the growth and expansion of the interfacial IMCs, and increased the shear strength of the solder joint [38]. To be specific, the reinforcement with 76 nm Ag nanoparticles refined the microstructure by 49.1% and enhanced the microhardness by 12.2% compared to the standard Sn–Bi solder because the extent of the formation of the Cu–Sn IMC decreased from 0.394 to 0.339, suppressing the IMC thickness by 39.7% and improving the shear strength by 18.9% after reflowing at 220°C for 180 min. However, after the addition of both larger (133 nm) and smaller (31 nm) Ag nanoparticles, such thermomechanical properties improvements were lower than those of the solder having 76 nm Ag nanoparticles [38]. These improvements might have been due to refinement and dispersion strengthening and adsorption [38]. In fact, although the solder with smaller Ag nanoparticles should have had higher property improvements than those with larger ones, the agglomeration of the smaller sized Ag nanoparticles deteriorated the overall solder\'s properties and reduced the practical improvements [38]. Overall, an optimal particle size was proposed to balance the theoretical improvement and the agglomeration weakening; this size generated the best real improvement [38].
\nThe reinforcement effects of the Al2O3 nanoparticles in Sn–58Bi solder were investigated from the aspects of electromigration, shear strength, and microhardness [39]. The experimental results show that the Al2O3 nanoparticles significantly improved the mechanical performances of the solder joints. The addition of Al2O3 nanoparticles reduced the thickness of the Bi IMCs along the interfacial layers [39]. More specifically, the growth rate of the IMC thickness according to the addition of Al2O3 nanoparticles decreased by 8% compared with that of pristine solder [39]. Furthermore, the microhardness of Al2O3-containing solder exhibited better performance than that of pristine solder according to aging time [39]. On the other hand, the addition of Al2O3 significantly improved the shear strength of the solder joint after aging for 48 and 288 h [39]. More specifically, after the solder was aged for these time periods at 85°C, the amplitudes of the shear strength increased by 3.5% and 2.4%, respectively, because unlike the smooth surface of the pristine solder, the surface of the Al2O3-containing solder showed a ductile failure (fractured) state [39].
\nTo improve the mechanical behaviors of a Sn–58Bi/Cu joint, a minor amount of elemental Zn was alloyed into the Cu substrate [40]. The interfacial IMC growth and bending properties of Sn–58Bi/Cu and Sn–58Bi/Cu–2.29Zn were studied according to the effect of isothermal liquid and solid aging [40]. Although there was no significant change in the composition, thickness, or morphology of the interfacial IMC under liquid aging, the depressing of IMC growth at the interface between the Sn–58Bi solder and the substrate and the avoidance of the formation of Cu3Sn IMC, Kirkendall voids, and Bi segregation at the IMC/Cu interface were realized for the Cu–Zn substrate under isothermal solid aging [40]. Joint strength and fracture behavior were also improved when using the Cu–Zn substrate [40]. There was no obvious decrease in the joint strength, and fracturing during bending was found mainly to occur in the solder matrix with ductile fracture mode or along the solder/IMC interface with partly brittle fracture mode for the Cu–Zn joint; these behaviors can be compared with the dramatically decreased joint strength and brittle fracture mode that occurred along the interface between IMC and Cu in Sn–Bi/Cu joints after aging [40].
\nSn–57.6Bi–0.4Ag solder was reinforced with tungsten (W) nanoparticles at a concentration of 0.5 wt.% [41]. Due to the dispersion of W nanoparticles and the consequently refined microstructure, the mechanical properties of the solder alloy were enhanced, as indicated by the 6.2% improvement in the microhardness [41]. During electromigration, the segregation of the Sn-rich and Bi-rich phases and the accumulation of an (Au, Ni), (Sn, Bi)4 layer at the cathode interface were also alleviated by the addition of W nanoparticles, which improved the electromigration resistance [41].
\nThe tensile properties of eutectic Sn–Bi, Sn–Bi–0.5In, and Sn–Bi–0.5Ni solder alloys, and their shear strength as Cu/solder/Cu joints were investigated [15]. The addition of 0.5 wt.% Ni decreased the elongation property of the Sn–Bi alloy because of the formation of Ni3Sn4 IMCs [15]. The In-bearing solder alloys exhibited the greatest elongation among all the tensile-tested solder alloys [15]. The eutectic Sn–Bi and Ni-bearing solder joints exhibited degraded shear strength owing to the formation of coarsened Bi-rich phases [15]. The thermally aged Sn–Bi solder joints on Cu substrates exhibited a harshly fractured surface structure in the IMC layers at the interfacial boundaries, whereas the thermally aged In- and Ni-containing Sn–Bi solder joints showed a smoothly fractured surface structure because of the growth suppression of Cu–Sn IMCs [15]. In particular, the as-reflowed In-containing solder joints had a dimple-like, fractured surface structure, indicating a ductile microstructure because the thermally aged In-containing solder joints retained their ductile property well, while both the coarsened, fractured surface structure and excessive IMC growth of the thermally aged Sn–Bi solder joints at the interfacial boundaries is able to explain their mechanical degradation [15].
\nFour different concentrations of Ni (i.e. 0.05, 0.1, 0.5, and 1.0 wt.%) were individually added to Sn–58Bi samples, and respective microstructure, tensile strength, elongation, and wettability of Sn–58Bi–xNi were subsequently measured [29]. The results indicate that Ni refined the microstructure of the solder matrix and induced the formation of the Ni3Sn4 phase; furthermore, the formation and then continuously increasing concentration of Ni3Sn4 were proportional to the increase of Ni added to the solder [29]. Thus, the optimal concentration of Ni added to enhance the solder\'s tensile strength should be less than 0.1 wt.% [29]. Nevertheless, the elongation of the alloy was in fact inversely proportional to the increase of the added Ni content, although the appropriate incorporation of Ni contributed positively to the wettability of the solder alloy [29].
\nWhen the In content increased to 4% in the Sn–Bi alloy, tensile test results showed that the tensile strength increased slightly with the increase of added In, while the elongation first increased remarkably and then decreased after the addition of 2.5 wt.% In [13]. The diffused In was confirmed to participate in interfacial reactions, thereby forming Cu–Sn–In IMCs and affecting the wettability of the Sn–Bi solder on the Cu substrate [13]. Tensile strength changed slightly with increasing In addition, while the elongation increased remarkably with the addition of 2.5 wt.% In [13].
\nThe interfacial reaction kinetics, tensile strength, and creep resistance of the Sn–58Bi–xZn (x = 0.0 or 0.7 wt.%) solder samples during liquid-state aging were investigated [33]. With the addition of 0.7 wt.% Zn, ultimate tensile strength (UTS) values of the eutectic Sn–Bi solder increased by 6.05 and 5.50% after soldering and aging, respectively; those values for the Cu/Sn–Bi/Cu solder joints also increased by 21.51 and 29.27%, respectively [33]. The increase in strengthening of the Cu/Sn–Bi–xZn/Cu solder joints can be attributed to the phase transformation at each Cu/IMC/solder interface due to the formation of finer Bi grains according to the addition of Zn [33].
\nThe effect of Sb content on the mechanical properties of Sn–Bi solders was studied [18]. The mechanical properties of the solders/Cu joints were also evaluated [18]. The results show that the ternary alloy solders contain eutectic structures resulting from a quasi-peritetic reaction [18]. With the increase of the Sb content, the size of the eutectic structure increases [18]. A small amount of Sb has a large impact on the wettability of the Sn–Bi solders [18]. Reaction layers form during the spreading process [18]. Sb is detected in the reaction layer, while Bi is not detected [18]. The total thickness of the reaction layer between the solder and Cu increases with increased Sb [18]. The shear strength of the Sn–Bi–Sb solders also increases as the Sb content increases [18].
\nThe mechanical properties of the melt-spun Bi–42Sn, Bi–40Sn–2In, Bi–40Sn–2Ag, and Bi–38Sn–2In–2Ag alloys were studied using dynamic resonance and Vickers indentation techniques at room temperature and compared to the mechanical properties of the traditional Sn–Pb eutectic alloy [42]. The results show that the crystallographic structure of the Bi–42Sn alloy presents as a combination of body centered tetragonal Sn and rhombohedral Bi [42]. The two ternary alloys exhibit additional constituent phases of SnIn19 for Bi–40Sn–2In and Ag3Sn for Bi–40Sn–2Ag alloys [42]. Attention has been paid to the role of IMCs in the mechanical and creep behavior [42]. The In- and Ag-containing solder alloys exhibited a good combination of higher creep resistance as compared with the Pb–Sn eutectic solder alloy [42]. This was attributed to the strengthening effect of Bi in the Sn matrix and the formation of InSn19 and Ag3Sn IMCs, which act as grain refiners in the matrix material [42].
\nSn–57.6Bi–0.4Ag solder joints with different contents of CNTs and Ni–CNTs were investigated [35]. In particular, it was possible to improve the mechanical properties of the Sn57.6Bi0.4Ag solder joints by the addition of either CNTs or Ni–CNTs, and those with the addition of 0.05 wt.% CNTs or 0.07 wt.% Ni–CNTs showed the best mechanical performance [35]. With the addition of either CNTs or Ni–CNTs, the solder joints had rougher, fractured surface structures, resulting in better bonding properties. Although reinforcement with either CNTs or Ni–CNTs improved the mechanical performance of solder joints, Ni–CNTs worked much better [35]. Ni coating was proven to significantly inhibit the aggregation of CNTs, which can induce cracks and wetting problems and even deteriorate the strength of solder joints [35].
\nSn–Bi composite solders containing Ni–CNTs were successfully synthesized [43]. The mechanical properties of Sn–Bi with different weight percentages of Ni–CNT were investigated [43]. The UTS and elongation of the Sn–Bi–0.05(Ni–CNT) solder with the optimized amount (0.05 wt.%) of Ni–CNTs increased remarkably because the CNTs and Ni3Sn4 enhanced the wettability and bondability of the composite solder [43]. However, because of the presence of CNT clusters and the intrinsic brittleness of IMCs, the UTS and elongation degraded with increased addition of Ni–CNTs [43]. That is to say, the UTS of the solder joint reached its maximum value with 0.05 wt.% Ni–CNTs addition and then degraded after increased addition of Ni–CNT [43]. Moreover, the tensile strength of the composite solder was much higher than that of the pristine solder, and subsequently, the creep resistance and hardness of the Sn–Bi–0.05(Ni–CNT) solder increased significantly compared to those of the Sn–Bi solder [43]. However, the hardness and the creep performance also decreased with 0.1 and 0.2 wt.% CNT content due to the same reasons mentioned above [43]. The CNT clusters and pore formation in the presence of the IMC with its intrinsic brittleness contributed to the decreases of hardness and creep performance [43].
\nThe mechanical strength and ductility of the eutectic Sn–Bi solder alloy were dependent on the incorporation of MWCNTs [44]. Mechanical test results show that the bending strength of the Sn–Bi–0.03CNT composite increased by 10.5% compared to that of the reference Sn–Bi alloy, which can be attributed to the reduction in Sn-rich segregation and to grain refinement [44]. In particular, the toughness of the Sn–58Bi–0.03CNT composite increased by 48.9% compared to that of the unreinforced Sn–Bi solder alloy [44]. In addition, corresponding fracture surface comparison between the Sn–58Bi–0.03CNT composite and the monolithic Sn–58Bi alloy was performed to identify the influence of CNTs on the fracture behavior [44].
\nThe effects of graphene nanosheets on the mechanical properties of the Sn–58Bi–0.7Zn solder joint were investigated [45]. Experimental results and finite element simulations showed that the best mechanical property improvement came from the 0.076 wt.% graphene nanosheet-doped Sn–58Bi–0.7Zn sample [45]. For the thermal aging samples, the UTS of the solder joint was also increased by 2.04% [45].
\nThe mechanical properties (the stress expansion and strain distribution during a single lap shear test) of the Sn–Bi–graphene nanocomposite according to the weight ratio of graphene were simulated based on the theoretical calculations of the finite element method [46]. The strength of the joint was found to be mainly influenced by the shear stress; initial cracking was found to occur at the edge of the joint [46]. The shear modulus of the Sn–Bi–graphene nanocomposite was 192% greater than that of the pure Sn–Bi alloy, when the content of graphene increased to 1.0 wt.% [46]. Stress concentration was found to exist near the edge of the graphene, where initial failure may occur [46].
\nGraphene nanosheets were successfully incorporated at various percentages (0, 0.01, 0.03, 0.05, or 0.1 wt.%) into Sn–58Bi solder [19]. The tensile properties, wettability, corrosion resistance, microhardness, and creep behavior were subsequently improved [19]. Tensile and nanoindentation tests reveal that the composite solder with 0.1 wt.% graphene nanosheets leads to enhancements of about 14 and 38%, respectively [19]. With 0.01 wt.% graphene nanosheet addition, the elongation is 49% greater than that of the pure Sn–58Bi solder alloy [19]. The creep performance and the corrosion resistance are all enhanced by addition of graphene nanosheets [19]. The mechanism of enhancement of the graphene nanosheets of the performance of the composite solder alloy is also analyzed in this work [19]. Tensile tests reveal that the UTS of the solders rises gradually with graphene nanosheet addition; there is a 14% enhancement of tensile strength for the Sn–58Bi–0.1graphene nanosheet [19]. The huge enhancement of 49% in the elongation of Sn–58Bi–0.01graphene nanosheet and the establishment of a brittle to ductile fracture mode are induced by the strengthening effect of graphene nanosheets [19]. The wettability is improved with graphene nanosheet addition because the nanosheets lower the interfacial surface energy between the solder and the substrate [19]. Moreover, the corrosion resistance is distinctly enhanced in the Sn–58Bi–0.1graphene nanosheet, and this material retains a lower corrosion rate than that of Sn–58Bi [19]. The hardness and creep resistance leads to an obvious improvement due to the addition of graphene nanosheets [19]. The hardness is enhanced by 38%, when the addition of graphene nanosheets increases to 0.1 wt.% [19]. The enhancement of the creep behavior is further illustrated by the variation of the creep mechanism in the solder alloys [19]. Among the composite solders synthesized, the Sn–58Bi–0.1graphene nanosheet provides the best tensile strength and hardness with decreased ductility (Table 4) [19].
\nCompositions | \nAdditives | \nCauses | \nResults | \nReferences | \n
---|---|---|---|---|
Sn–58Bi | \n0.05 wt.% Cu6Sn5 nanoparticles | \nBrittle IMC nanoparticles | \nCreep resistance | \n[36] | \n
Sn–58Bi | \n76 nm Ag nanoparticles | \nRefinement and dispersion | \nMicrohardness and shear strength | \n[38] | \n
Sn–58Bi | \nAl2O3 nanoparticles | \nReinforcement effect | \nElectromigration resistance, shear strength, and microhardness | \n[39] | \n
Sn–58Bi/Cu and Sn–58Bi/Cu–2.29Zn joints | \nAlloying 2.29 wt.% Zn to Cu substrate | \nSuppression of Cu3Sn formation, Kirkendall voids, and Bi segregation at the IMC/Cu interface | \nAdhesion strength | \n[40] | \n
Sn–57.6Bi–0.4Ag | \n0.5 wt.% W nanoparticles | \nRefined microstructure | \nElectromigration resistance and microhardness | \n[41] | \n
Sn–58Bi, Sn–58Bi–0.5In, and Sn–58Bi–0.5Ni | \n0.5 wt.% In or Ni | \nNi3Sn4 IMC formation at the grain boundaries | \nShear strength degradation of Sn–58Bi–0.5Ni and improvement of Sn–58Bi–0.5In | \n[15] | \n
Sn–58Bi | \n0.05, 0.1, 0.5, or 1.0 wt.% Ni | \nNi3Sn4 IMC formation | \nWetting behavior | \n[29] | \n
Sn–58Bi/Cu joint | \n2.5 wt.% In addition to the solder | \nCu–Sn–In IMCs | \nWetting behavior | \n[13] | \n
Sn–58Bi | \n0.0 or 0.7 wt.% Zn addition to the solder | \nLiquid-state aging | \nUltimate tensile strength | \n[33] | \n
Sn–58Bi/Cu joint | \nSb addition | \nIncreasing size of the grain | \nWetting behavior | \n[18] | \n
Sn–58Bi | \n2 wt.% In, 2 wt.% Ag, or each 2 wt.% In and Ag | \nSnIn19 and Ag3Sn IMCs (grain refiner) | \nCreep resistance | \n[42] | \n
Sn–57.6Bi–0.4Ag | \n0.05 wt.% CNTs or Ni–CNTs | \nNi3Sn4 IMCs | \nUTS and elongation | \n[43] | \n
Sn–58Bi | \n0.03 wt.% MWCNTs | \nReduction of Sn-rich segregation and refinement | \nBending strength | \n[44] | \n
Sn–58Bi–0.7Ag | \nGraphene nanosheets | \nFinite element simulation | \nUTS | \n[45] | \n
Sn–58Bi | \nGraphene | \nFinite element method | \nShear modulus | \n[46] | \n
Sn–58Bi | \n0, 0.01, 0.03, 0.05, or 0.1 wt.% graphene nanosheets | \nReinforcement effect | \nTensile strength, wettability, corrosion resistance, hardness, and creep behavior | \n[19] | \n
The improvement of various mechanical properties of the low melting temperature solders.
The electrical and thermo-mechanical properties of many different low melting point solders are affected by a variety of processing factors, such as the reflow temperature, time, flux used and its effectiveness, and temperature of measurement [15, 36, 37, 40, 41, 45]. Furthermore, the change of chemical composition of solders according to the addition of supplementary additives is also considered as a main factor that modifies or even improves a solder’s electrical and thermo-mechanical properties [15, 36, 37, 40, 41, 45]. Three main methods are used to improve the electrical and thermomechanical performance of low melting point solders: (i) doping with a small amount of certain elements via diffusion reactions, (ii) alloying with a large amount of certain elements, and (iii) reinforcing with metal or ceramic elements. Sometimes, (iv) all of these methods are combined for the enhancement of the intended properties of low melting temperature solders.
\nTransient liquid phase bonding was conducted using the Sn–Bi solder with 30 wt.% Cu particles added [37]. However, this process caused the melting point of the solder joints to increase from 139 to 201°C; In addition, the solder joints contained large voids, resulting in a considerable degradation in shear strength [37].
\nOn a Cu substrate, the conventional Sn–58Bi solder was alloyed with 0.7 wt.% Zn to improve the interfacial reaction, tensile strength, and creep resistance during liquid-state aging [37]. However, the overgrown IMC layers between the Sn–58Bi solders and Cu substrates significantly degraded the reliability of the electronic products [37].
\nLin et al. added minor amounts of Ga, ranging from 0.25 to 3.0 wt.% to Sn–58Bi solder [14]. As a result, the growth of IMC layers was effectively suppressed [14].
\nHu et al. fabricated an Sn–58Bi composite solder reinforced with Al2O3 nanoparticles to slow down electromigration and to improve the shear strength and microhardness [39].
\nFour different concentrations of Ni (0.05, 0.1, 0.5, and 1.0 wt.%) were individually added to the Sn–58Bi solder [29]. The optimal concentration of Ni necessary to enhance the tensile strength of the alloy was 0.1 wt.%, but the elongation of the alloy was inversely correlated to the Ni content [29].
\nWojewoda-Budka and a coworker demonstrated excellent diffusion soldering process results for Bi–22 at.% In on Cu interconnections; this was proved by the presence of Cu11In9 phase present in the Cu/In–22Bi/Cu interfaces in the temperature range of 85–200°C [47].
\nGraphene nanosheets were successfully incorporated at various percentages (0, 0.01, 0.03, 0.05, and 0.10 wt.%) into Sn–58Bi solder; the microstructure, tensile properties, wettability, corrosion resistance, hardness, and creep behavior were significantly improved [19].
\nSun et al. introduced a low melting temperature Sn–57.6Bi–0.4Ag solder reinforced with different concentrations of MWCNTs or Ni-coated MWCNTs [35]. With the addition of MWCNTs and Ni–MWCNTs, the fractured surface of the solder joints became rougher, leading to a better bonding structure [35]. Though both MWCNTs and Ni–MWCNTs have the capability to improve the mechanical performance of solder joints, Ni–MWCNTs worked much better [35]. The Ni coating was proved to significantly inhibit the aggregation of MWCNTs, which can solve cracks and wetting problems and even improve the strength of solder joints [35].
\nA recent trend in solder research mentioned that low melting temperature solder materials and their nanocomposite materials will be suitable for flexible interconnection applications in the near future. Thus, fabrications and/or syntheses, as well as elaboration of the electrical and thermomechanical properties, of various low melting temperature solder materials are discussed in detail. The various determination factors regarding the electrical and thermomechanical properties of solder materials are also elucidated with theoretical and experimental support. Subsequently, a promising approach to enhancing the performance of solder materials using supplementary additives, such as nanostructures, nanocomposites, alloying, and doping, is described with examples. It is possible to conclude that low melting temperature solders may enable significant advancement in interconnecting components in various applications and soldering technologies for the flexible microelectronic packaging industry.
\nThis study was supported financially by Fundamental Research Program of the Korea Institute of Materials Science (KIMS). This work was also supported by the National Research Council of Science & Technology (NST) grant by the Korea government (MSIP) (No. CAP-12-6-KIMS).
\nWith regard to competing financial interests, the authors declare that they have none.
Legumes are a cheap and healthy source of nutrition because of their high protein content and complete constituent components, such as fats, essential amino acids, complex carbohydrates, vitamins, and minerals or dietary fibre. This high protein content plays an essential role in producing functional compounds such as bioactive peptides (BPs) that benefit the health and treatment of chronic diseases. For example, BP from legumes is used as an antioxidant compound to prevent degenerative diseases such as atherosclerosis, coronary heart disease, diabetes mellitus, and cancer [1, 2]. The number of deaths due to NCDs (non-communicable diseases), especially cardiovascular disease, cancer, chronic respiratory diseases, and diabetes, increases globally, both in low-income and rich countries. As a result, NCDs are still the cause of most global deaths each year [3]. One way to reduce the risk of NCD is controlling hypertension, regulating diet and obesity.
Protease enzymes have an essential role in producing BP as a result of protein hydrolysis. Food processing, microbial fermentation, germination, or other process involving protease enzymes are examples of proteolytic processes. The involvement of protease enzymes in producing BP is significant because BP is mainly composed of 2–20 amino acids [4]. Some countries have healthy food products from legumes. Examples of fermented foods such as natto [5], douchi [6], tempe [7], and others, have antihypertensive activity. Fermented foods represent, on average, one-third of total food consumption [8]. Fermented food has a delicious taste, easy to digest, nutritious and has beneficial properties. Such as antidiabetic, hypocholesterolemic, and anti-inflammatory activities [8, 9].
Many researchers have proven (both in vitro and in vivo using experimental animals) that BP from legumes has functional properties as a healthy food. However, this functional effect depends on the stability of BP to withstand the action of digestive enzymes while in the digestive tract on its way to reach the target organs [10]. In this target organ, BP will act to provide health effects for the body. One of the determining factors to be bioavailable is the number of amino acids, hydrophobic amino acid content, and resistance to digestive enzyme activity [11]. This chapter aims to describe the quality of various legumes, the BP of legumes and their effects on health. Also, an explanation of the factors that affect the stability, absorption, bio-availability and bio-activity of BP and food technology to develop functional food.
One of the excellent sources of essential amino acids and protein is legumes. As a source of bioactive peptides (BPs), an ingredient must have a high enough protein content. In addition, legumes also contain many components needed for body health, such as antioxidant compounds, resistant starch, dietary fibre and others [12]. However, it is a fact that the nutritional content and phytochemical composition among legumes vary widely, as shown in Table 1. The differences in their genetics, varieties, geographical location and climatic conditions may cause the nutritional content variation [18].
No | Legumes sources | Protein | Amino acid hydrophobic | ||
---|---|---|---|---|---|
(db, % w/w) | Reference | (% w/w protein) | Reference | ||
1 | Soybean, | 35.35–39.80 | [13] | 37.70 | [14] |
2 | Jack bean, white, | 22.80–35.30 | [14] | 8.60–43.50 | [14] |
3 | Sword bean, red, | 32.4–35.0 | [15] | 26.62–29.47 | [15] |
4 | Cowpea, | 20.90–24.70 | [16] | 8.46 | [16] |
5 | Bambara groundnut, | 17.00–17.30 | [16] | 6.45 | [16] |
6 | Velvet bean, White, | 28.82 ± 0.14 | [17] | 34.14 | [17] |
7 | Velvet bean, Black, | 26.26 ± 0.07 | [17] | 32.79 | [17] |
8 | Kidney beans, | 21.80–29.20 | [18] | 7.96 | [16] |
9 | Lima beans, brown, Phaseolus luna tus | 28.06 | [7] | 4.68 | [7] |
10 | Mung bean, Phaseolus radiata | 26.80 | [19] | 39.75 | [20] |
11 | Chick pea, Cicer Arieti num | 19.68–22.75 | [16] | 35.3 | [21] |
Protein and hydrophobic amino acid content of several legumes.
The level of hydrophobic amino acids is the sum of the data available in the reference sources used.
In general, the protein content of legumes ranged from 17.0 to 39.8% (w/w). Soybean is the legumes that have the highest protein content. Soybean is also the most studied legume regarding its function on health. According to FAO [22] world soybean production in 2019 was 333,671,692 tonnes (the highest among the types of legumes produced), of which Brazil produced 34.25% as the world’s No. 1 producer country. Apart from soybean, some legumes also have a high protein content as a source of BPs, such as jack beans, velvet beans, lima beans, mung beans, and kidney beans (Table 1).
In addition to the protein content, it is also necessary to pay attention to the amino acid composition in choosing ingredients. Peptides with hydrophobic amino acids (Tyr, Phe, Trp, Ala, Ile, Val, and Met), positively charged amino acids (Arg and Lys), or contain Pro at the C end will have higher biological activity. For example, inhibition of ACE enzymes [23], Diabetes mellitus type 2 (T2DM) inhibitory activity [24], or other biological functions. Angiotensin-Converting Enzyme Inhibitor (ACEI), is a BP that affects lowering blood pressure. Meanwhile, DPP-IV inhibitors are compounds that can inhibit dipeptidyl peptidase-IV, an enzyme associated with T2DM disease [25]. So the presence of hydrophobic amino acids in short-chain peptides (between 2 and 20 amino acids in length) [4] is related to biological activities beneficial to health. Soybean, jack bean, velvet bean and mung bean are legumes that have high hydrophobic amino acid content (Table 1). Enzymatic breakdown through food processing produces short-chain peptides. For example, fermentation (to produce tempeh, soy sauce, natto, miso, douche, or other legume fermented products), germination (mung bean sprouts, soybean sprouts, or other sprouts), or other processes can break the polypeptide chain.
Apart from these benefits, legumes contain substances that are considered anti-nutritional compounds [26]. Despite having a high protein content, some toxic anti-nutritional substances limit the use of legumes. Food processing, such as soaking (hydration), cooking, autoclaving, germination, and combination, could reduce or eliminate anti-nutritional compounds [27, 28]; these processes can increase the digestibility value of protein ingredients. Table 2 shows some of the anti-nutritional compounds present in some legumes. Kalpanadevi and Mohan [26] said that the soaking process and continued germination was less effective in removing anti-nutrients. However, the process would be effective if the germination process was extended (96 hours) or continued with the heating process (or autoclaving process). With this combination process, the effect of anti-nutritional compounds can be eliminated, such as phenolics, tannins, hydrogen cyanide, phytic acid, trypsin inhibitors, oligosaccharides and Phyto-hemagglutination activity.
No | Legume sources | Antinutritional compound | References | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Phenol (%) | Tannin (%) | L-DOPA (%) | Phytic acid (%) | Trypsin inhibitor (TIU/mg protein) | HCN (ppm) | Oxalate (%) | Total oligosaccharide (%) | |||
1 | Cowpea, | 1.21 | 0.38 | 2.46 | 0.4 | 26.48 | 2.2 | NA | NA | [26] |
2 | Velvet bean, Black, | 2.84 | 0.26 | 3.64 | 0.45 | 43.1 | 3.1 | NA | NA | [17] |
3 | Velvet bean, White, | 3.13 | 0.34 | 3.24 | 0.42 | 43.5 | 2.1 | NA | 4.49–6.08 | [17, 29] |
4 | Sword Bean, red, Canavalia gladiate jacq DC. | 1.21–1.41 | 0.16–0.20 | 2.32–2.64 | NA | 30.43–34.34 | NA | NA | NA | [16] |
5 | Kidney bean, | NA | 0.54–2.88 | NA | 1.68–2.41 | 3.65 | NA | NA | 12.51 | [19, 30] |
6 | Chick pea, | NA | 0.01–0.05 | NA | NA | NA | 13.5–40.5 | 0.18–0.45 | NA | [17] |
7 | Jack Bean, white, | 3, 83 | 0.083 | 1.7 | 0.90 | NA | 59.95 | NA | 8.17 | [28, 31] |
8 | Soybean, | 1.40–3.62 | 1.11–1.88 | NA | 0.51–2.45 | 23.67 | NA | NA | 8.30–10.11 | [27, 32] |
Anti-nutritional compounds in legumes.
NA, data not available in the references used.
Data is prepared and recalculated so that it has the same units.
Other researchers stated that the fermentation process is also very effective for reducing/removing anti-nutritional compounds because the fermentation process is a combination of several processes, including soaking, heating, and proteolytic hydrolysis by starter microbes [31]. For example, the process of fermenting koro bean tempe (
Bioactive peptides (BPs) are tiny fragments of dietary protein, consisting of 2–20 amino acids, have a molecular weight of less than three kDa, and promote health benefits. After entering the body, BPs can be absorbed in the intestine, carry out various metabolic pathways, and perform various physiological functions [4, 35, 36]. Several researchers have reported that legumes have various biological activities good for body health (Table 3).
Legumes | Amino acid sequence | Reference | |
---|---|---|---|
Kidney bean, | INEGSLLLPH | [9] | |
Soybean, germinated | NNDDRDS, LSSTEAQQS, NAENNQRN, QQQQQGGSQSQ, EEPQQPQQ, IKSQSES | [37] | |
Cowpea, | TTAGLLE | [38] | |
Black bean, | AKSPLF, ATNPLF, FEELN, LSVSVL | [39] | |
Kidney bean, | FVVAEQAGNEEGFE | [9] | |
Mung Bean, | KDYRL, VTPALR, KLPAGTLF | [40] | |
Soybean, | VLIVP, LAIPVNKP, LPHF, NVVGPLV, YLAGNQ, IPPGVPYWT, DQTPRVF, ASYDTKF, DTKF, PNNKPFQ, RPSYT | [41, 42, 43, 44, 45] | |
Soybean protein, | IVF, LLF, LNF, LSW, LEF | [46] | |
Soybean germinated | RNLQGENEEEDSGA | [37] | |
Fermented soybean, natto | VAHINVGK, YVWK | [5] | |
Fermented soybean, soy sauce | GY, SY | [47] | |
Garden pea, | LRW | [48] | |
Pigeon pea, in silico | VVSLSIPR | [49] | |
Kidney bean, | SGGGGGGVAGAATASR | [9] | |
Soybean, | LPYP, IAVPGEVA, IAVPTGVA, YVVNPDNDEN, YVVNPDNNEN, LPYPR | [50, 51, 52] | |
Soybean protein, | SFGYVAE | [53] | |
Black bean and cowpea, in silico | YAAAT | [54] | |
Soybean, | LLPHHADADY, LLPHH, LVNPH, DHQN, TTYY, LQSGDALRVPSGTTYY | [42] | |
Soybean, | RPSYT | [43] | |
Soybean, | IIVVQGKGAIGF, ASRGIRVNGVAPGPVWTPIQPA, IIIAQGKGALGV, | [42] | |
Soybean, | IKAFKEATKVDKVVVLWTA, PGTAVFK | [55] | |
Black bean ( | IAISISGLL, CNKY, YETN, QAEEEF, MSAMSNAAA, DLPYSCR, ATL, NLG, EDAY, GYDHPMGGL, PVNF, EEAK, LGAL, DLK, LVVL, VPTK, TGVI, TTW, MEL, FNL, GFTPL, KYGDKSVY, IPVL, KTCENL, GGSSDKR | [56] | |
Soybean (Glycine mox) | Lunasin | [57] | |
Soybean ( | Lunasin | [58] | |
Common beans ( | ANEIYFSFQRFNETNLILQR | [59] | |
Chickpea (Cicer anetinum) | ARQSHFANAQP | [60] |
The amino acid sequence of several bioactive peptides from legumes.
The hydrolysis of legumes protein can produce these BPs. The enzymatic hydrolysis process occurs in the food processing process, for example, in the fruit ripening process, the fermentation process (producing soy sauce, tempe, natto, and other fermented products), or the germination process (producing soybean sprouts, green bean sprouts, and sprouts products others). In addition, the protein breakdown process can also be carried out by in vitro enzymatic hydrolysis, for example, using the alcalase in legume protein. Some examples of enzymatic hydrolysis are soybean hydrolysis (
BPs can perform their activities and roles based on their structural properties, composition and amino acid sequence [62]. Biologically, the active peptides have similar structural properties, including the length of the amino acids, containing hydrophobic amino acids, and resistance to proteolysis [11]. For example, BPs with antioxidant activity have a length of 5–16 amino acids [63]. The structure of ACE inhibiting BPs contains arginine or lysine residues at the C-terminal will affect their activity [11]. Therefore, selecting the protease enzyme to form BPs is essential to produce biologically active peptides. For example, the Carlsberg enzyme subtilysin will hydrolyse peptide bonds with broad specificity to produce peptides with C terminal in the form of hydrophobic amino acids such as Phe, Tyr, Trp, Leu, Ile, Val and Met [64]. In addition, because of their relatively small size and high specificity, BPs can inhibit protein–protein interactions [65]. Some examples of the functional properties possessed by BPs are anti-hypertensive [66], antioxidants [67], hypo-cholesterolemia [68], antimicrobials [69], anti-inflammatory [70, 71], anti-cancer [59], and other functional properties. One type of BPs can have more than one functional property [9, 65]. To date, researchers are still developing comprehensive studies and reviews to confirm the therapeutic effect of BPs. This chapter will discuss the BPs of legumes and their functions.
Increased blood sugar levels are signs of diabetes caused by decreased insulin secretion, impaired insulin function, or both. In patients with T2DM, the body does not respond adequately to insulin action and the blood glucose level increases, a condition known as hyperglycemia [72]. Changing diet is one way of treating diabetes, besides losing weight, exercising, or taking drugs to increase glucose homeostasis [25]. Side effects from synthetic antidiabetic drugs are gastrointestinal disorders [73]. Other side effects are hypoglycemia and weight gain [74].
Meanwhile, some patients are intolerant of the drug [75]. Therefore, research to find BPs from food as a safe antidiabetic has recently increased to overcome these side effects [76]. Measuring the inhibitory activity of DPP-IV is one way to determine whether BPs have an antidiabetic activity or not. The role of the DPP-IV enzyme is to inactivate incretins, especially GLP-1 and GIP. GLP-1 is a glucagon-like peptide, while GIP is a glucose-dependent autotrophic insulin peptide. Incretin is a hormone that vitalising insulin secretion. So the mechanism commonly used to control T2DM is to measure how much DPP-IV inhibition is [77].
Several low molecular weight BPs can induce insulin stimulation in blood intake, for example, the peptides present in fermented soybeans [78] or fermented kidney beans [9]. Some BPs that are isolated from black bean (
Controlling hypertension is essential to reduce the risk of cardiovascular complications such as coronary heart disease (which causes heart disease) and stroke, congestive heart failure, irregular heart rhythm, and renal failure [3, 79]. A healthy diet is a way to control hypertension. Eating foods high in BPs is very healthy. Several studies have shown that food ingredients derived from legumes have an anti-hypertensive function. The preparation of BPs uses three ways: fermentation of materials into fermented products, germination, and enzymatic hydrolysis. Table 3 shows some of the research results.
The anti-hypertensive activity was measured by measuring the inhibitory activity of the ACE (Angiotensin I-converting Enzyme). The ACE will cut angiotensin I to produce angiotensin II (vasoactive peptide). This angiotensin II compound will bind to receptors on the walls of blood vessels causing contraction of blood vessels so that blood pressure rises [80]. The presence of BPs will bind to the ACE enzyme, thus inhibiting the action of ACE, and as a result, blood pressure can drop. Some legumes that are recognised to contain BPs that lower blood pressure include garden beans (
Research on anti-hypertensive BPs from food is still being studied [65]. Anti-hypertensive BPs (isolated from food) have a higher tissue binding affinity than synthetic drugs, resulting in slower tissue loss [83]. For vigorous anti-hypertensive activity, the position of specific amino acid residues is critical. For example, valine and isoleucine are essential for ACE inhibition [84]. Increased ACE inhibitory activity occurs when the C-terminal is Proline [84]. Therefore, the strategy to produce peptides with high anti-hypertensive activity is to hydrolyse protein to produce proline containing peptides.
Many researchers have studied and reviewed the ability of BPs as cholesterol-lowering agents [65]. The human body needs healthy cholesterol levels to produce vitamin D and steroid hormones, and bile acids. However, arteriosclerosis can occur when cholesterol in the blood forms plaque in the arteries. As a result, it can reduce oxygen supply to the heart, which leads to cardiovascular disease. While chemicals that lower blood cholesterol can cause liver damage or failure, myopathy [85] and diabetes [86, 87], or some people are sensitive to statins (cholesterol-lowering drugs) [88]. Therefore, the research for BPs that can lower cholesterol has increased over the years [65]. Table 3 shows BPs in legumes (such as red beans and soybeans with 4–16 amino acids) with hypocholesterolemic activity.
Cholesterol reduction by peptides can occur due to inhibition of cholesterol micelle formation, inhibition of lipase activity and strong bile acid-binding [89]. Peptides from fermented soy milk show the ability to bind bile acids [90]. The solubility of cholesterol in lipid micelles will be reduced due to BPs [91], resulting in inhibition of cholesterol absorption in Caco-2 cells with one layer. For example, peptides from cowpeas can inhibit HMGCoA reductase and reduce the dissolution of cholesterol micelles in vitro [92]. A 36% reduction in plasma cholesterol levels could occur in the livers of rats consuming the a’-subunit. The tight binding of BPs with taurocholate, deoxytaurocholate, and glycodeoxycholate can also lead to decreased cholesterol absorption in the intestine [93]. Soybean peptides (LPYP, IAVPGEVA and IAVPTGVA) can activate the LDLR-SREBP 2 pathway to increase LDL uptake effectively. For moderate hypercholesterolemia, 30 g/ml lupine protein consumption effectively reduced the Proprotein Convertase Subtilisin/Kexin type 9 enzyme (PCSK9). Inhibiting HMGCoA reductase activity on HepG2 cells may explain the hypocholesterolemic effect of lupine protein hydrolysate [94]. In addition, peptides cause the regulation of lipoprotein b-VLDL cholesterol receptors to increase in rat liver [95].
The antioxidant properties of peptides have more to do with their composition, structure, and hydrophobicity [62]. The amino acid sequence of these peptides can determine different biological activities. Amino acids Tyr, Trp, Met, Lys, Cys, and His are examples of amino acids that cause antioxidant activity [96]. BPs from some legumes have antioxidant properties, for example, soy peptides with 4–16 amino acids [42, 43] (Table 3). This table also shows that BP of Leu-Leu-Pro-His-His from soybean β-conglycinin hydrolysate has antioxidant properties. The amino acid leucine or proline at the N-end can increase its antioxidative activity [35]. Amino acids with aromatic residues can donate protons to electron-deficient radicals. This property enhances the radical scavenging character of amino acid residues. Amino acids in the C-terminal region can increase the antioxidant activity higher than in the N-terminal region. This increase in antioxidative activity relates to the nature of the electronic, hydrophobic, steric, and hydrogen bonding amino acids in the area [39]. Soy milk has significant antimutagenic and antioxidant activity. So fermented soy milk probably can prevent mutagenic and oxidative damage [97]. Consumption of douchi (fermented soy food) extract will increase the activity of SOD (Superoxide dismutase) in the liver and kidneys of mice. This consumption also reduces the serum TBARS (Thio Barbituric Acid Reactive Substance), which will increase catalase activity (CAT). These results may indicate the involvement of BPs and free amino acid components from douchi extract as antioxidants [98].
The ability of BPs as antimicrobial peptides (AMP) has also been widely researched and studied [65]. For example, Pina-Pérez and Ferrús-Pérez [55] studied AMP from several legumes against bacterial pathogens that cause foodborne diseases. AMP is generally active against a broad spectrum of microorganisms, including bacteria (Gram+ and Gram-), fungi, and viruses [99]. Some AMPs also show additional activity, such as antioxidant activity [100], immunomodulation [101] and wound healing activity [102]. Therefore, this AMP may be a better choice of antibiotics for pathogenic bacteria resistant to conventional antibiotics.
AMP has various characteristics, including amino acid length (between 12 and 50), amino acid composition, charge and position of disulfide bonds [103]. AMP isolated from soybeans showed that long-chain peptides had higher AMP activity than short peptides [55]. AMP interacts with microbes due to positive charges or hydrophilic and hydrophobic (amphipathic) terminal amino acids, recognised as a prominent structural motif. The charge, hydrophobicity and length of cationic AMP are directly related to their potential as antimicrobials [103]. AMP will cause changes in permeability and osmotic disturbances in bacterial cell membranes [104]. AMP can directly kill bacteria by creating pores through the bacterial cell membrane [101] or interacting with macromolecules in microbial cells [105]. The structure and sequence of peptide amino acids are the main factors for whether or not it is effective as an antimicrobial [104]. Some AMPs are rich in positively charged amino acids (arginine and lysine). Such AMP can enter microbial cells by inducing energy-dependent endocytic pathways such as micropinocytosis [106]. Table 3 shows some of the AMP amino acid sequences from soybeans.
Inflammation is a natural immune system reaction to fight disease. Inflammation is generally associated with cancer because it involves the interaction of various immune cells that can lead to signals of proliferation, growth and invasion of tumour cells [107, 108]. There are two pathways of inflammatory-cancer interaction, namely the extrinsic pathway (inflammation facilitates cancer development) and the intrinsic pathway (genetic changes causing cancer to stimulate the inflammatory process to support tumour development) [109]. Bastiaannet and co-workers [110] and Crawford [111] reported that anti-inflammatory therapy could reduce or prevent cancer risk. This report shows the interaction between inflammatory-cancer. So far, lunasin, VPY and -glutamyl peptides have anti-inflammatory activity [70]. Lunasin exerts an anti-inflammatory effect by inhibiting the Akt-mediated NF-kB pathway [57]. BPs from legumes, particularly soybeans, can regulate several inflammatory markers, which include prostaglandin E2 (PGE2), nitric oxide (NO), induced nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), cytokines, and chemokines [70]. BPs from
Many researchers are experimenting with cancer therapy using BPs from various legumes. The results are more promising, cheaper, and safer than cancer treatment using surgery, chemotherapy, or radiotherapy, which have adverse side effects due to the emergence of drug resistance and radio-resistance [113]. Extensive exploration has shown that a high intake of legumes can significantly reduce the risk of colorectal adenoma [114, 115] BPs with anti-cancer activity have a relatively low molecular weight (Table 3), as isolated from black soybean by-products have the sequence Leu/Ile-Val-Pro-Lys [116]. In comparison, lunasin from soybeans contains 43 amino acids [58]. The hallmark of lunasin is the Arg-Gly-Asp sequence which functions for adhesion to the extracellular matrix, and the 8 Asp sequence to bind chromatin [117]. Kim and co-workers [118] said that hydrophobic BPs isolated from soybeans could act as anti-cancer. Some legumes also have higher hydrophobic amino acids that are similar in levels to soybeans, such as mung bean, chickpea, and velvet bean (Table 1), thus potentially producing anti-cancer peptides.
The mechanism of inhibition of tumour growth by BPs varies depending on the variety of legume sources, namely by induction of extrinsic apoptosis [119], induction of chromatin condensation [59] or inhibition of inflammatory processes [120]. BP isolated from chickpea (
Bioaccessibility, stability, and bioavailability are the main concerns in utilising bioactive peptides (BPs) from food ingredients to remain active in maintaining a healthy body. Bioaccessibility is the first step in the digestive system so that nutrients/BPs out of the food tissue and transported across the intestinal epithelial barrier into the blood circulation system. BP transport processes may involve passive transport (paracellular or passive diffusion) or active routes [126]. During the nutrient transport process, the stability of the material must be kept high, so the bioavailability of nutrients is maintained to be utilised by target cells or tissues. In the digestive tract, nutrients are released from the food matrix and converted into chemical forms that can bind to and enter intestinal cells or pass between them. Dietary factors can also affect the bioavailability of the BPs contained. Interactions between peptides and components of the food matrix can modulate their digestibility and alter the absorption route of the peptide [10]. The release of nutrients in the small intestine starts from chewing, which involves digestive enzymes in the mouth and then in the stomach mixed with acids and enzymes in gastric juices. This whole process is a process for making nutrients biologically accessible [127].
Although the number of active components in the food consumed is abundant, it cannot necessarily prevent disease because it depends on the amount available to function in target organs or tissues [128]. Bioavailability is the number of bioactive compounds that organisms can use effectively [129]. For example, when food contact with the mouth or gastrointestinal tract, various interactions can affect the bioavailability of food nutrients (e.g., the presence of fat can increase the bioavailability of quercetin in food) [130]. In studying the role of bioactive compounds in human health, several factors can inhibit the bioavailability of the active components for use in target organs or tissues [131]. For example, fruit antioxidants mixed with macromolecules form a food matrix such as carbohydrates, fats, and proteins [132].
From a nutritional point of view, bioavailability refers to several nutrient fractions or bioactive compounds that are ingested and can reach the systemic circulation and can finally be utilised [133]. Besides that, bioavailability is the fraction of a nutrient stored or available for a particular physiological function [134]. Another definition, bioavailability, is the amount of active metabolite from the oral dose fraction reaching systemic circulation [135]. The bioavailability of oral BPs is limited because their release from the plant matrix is affected by: solubility in GI fluids, permeability in intestinal epithelial cells, enzymatic and chemical reactions in the GI tract [136]. Four essential steps are required to absorb bioactive compounds effectively: (a) release from the food matrix; (b) incorporation into bile salt micelles; (c) absorption by epithelial cells; and finally; (d) incorporation into the cyclomicron secretion into the lymphatic system.
The biological effects of a BP depend on its capacity to survive until it reaches the target organ. Thus, the main requirement of a BP is its stability or resistance to gastrointestinal enzyme hydrolysis, brush border and serum peptidase. Experimental evidence shows that the length of the peptide chain determines the ability of BPs to pass through the intestinal epithelium in humans by different mechanisms. For small peptides, it is possible to transport through active basolateral, while for large peptides through a transport mechanism mediated by exocytotic-vesicles [137].
However, many peptides are biologically active but are unlikely to be absorbed in the gastrointestinal tract via local effects or receptors that release hormones and cell signalling in the gut. Such BPs affect gastric emptying, gastrointestinal transport, nutrient absorption (amino acids, glucose, lipids) and composition of the colon microflora. They may also regulate food intake [138].
In addition to the presence of specific residues, charge, and molecular weight, hydrogen bonding potential and amino acid hydrophobic tend to affect the bioavailability resistance of BPs to proteases and enzyme hydrolysing peptides [11, 139, 140]. Lunasin, a BP isolated from soybeans and cereal (wheat, barley and rice), has 43 amino acids (MW 5.4 kDa), displays a helical structure and contains nine aspartic acid residues in the C-terminal region. Lunasin is highly bioavailable, heat-stable (100°C, 10 min), and anti-cancer against carcinogenic chemicals. In vivo digestibility of lunasin-fortified soy protein was studied in mice fed for four weeks [141].
During transit in the central digestive tract, the structural properties of the peptide will influence the stability of BPs, including molecular weight, charge, amino acid sequence, and hydrophobicity [126]. Tests using Sprague Dawley rats showed that the highest absorption of ACE inhibitor BPs was in the jejunum [7]. The results showed that BPs with 2–6 amino acids were easy to absorb than proteins and free amino acids [142]. Small (di- and tripeptide) and large (10–51 amino acids) peptides can pass through the intestinal barrier and exhibit their biological function at the target tissue level. However, as the molecular weight of BPs increases, their chances of passing through the intestinal barrier decrease further [143]. The presence of proline and proline hydroxyl will result in resistance of BPs to digestive enzymes, especially a tripeptide with Pro-Pro at the C-terminal [144]. In another study, the number of peptides in human plasma increased depending on the dose of the BP administered. Thus, it concluded that the saturation of BP transporters could affect the number of peptides that can enter the peripheral blood [145].
Encryption of BPs in their natural protein structure may protect these BPs from gastric digestion. Another way to protect BPs is to modify structural proteins such as phosphorylation of serine, threonine, or tyrosine can prevent hydrolysis by digestive proteases. As a result, protein or peptides have a greater chance of being absorbed in target organs or tissues [146]. Stability also depends on the degree of hydrophobicity/hydrophilicity. The more hydrophobic the structure, the more difficult it is to attack by proteases [147].
Therefore, it explained that the difference in bioavailability of BPs between in vitro and in vivo tests (after oral consumption), which may be smaller or larger, occurs due to an increase or decrease in BPs after being catalysed by gastrointestinal proteases. A simulation test of the gastrointestinal digestion process of several tempe legumes (
Finally, the use of BPs in nutraceutical and pharmacology for human health is still limited. For that, it is necessary to evaluate: (1) degradation of BPs by proteases in the digestive tract, which can affect bioaccessibility, stability, and bioavailability; (2) the existence of technology that allows modification of the structure of BPs such as (a) phosphorylation of amino acids in BPs to make them more resistant to hydrolysis by digestive enzymes; or (b) increase the amino acid hydrophobic at the N-terminal or C-terminal [150].
In general, protein-rich foods that undergo processing involving protease enzymes will produce peptides. However, not all peptides resulting from protein hydrolysis of foodstuffs will become bioactive peptides (BPs) beneficial to body health. The structural properties of BPs (composition, amino acid sequence, hydrophobic amino acid content, and resistance to digestive enzymes) will determine their beneficial functional properties [126], such as, example anti-diabetic, anti-hypertensive, cholesterol-lowering, antioxidant, and other functional properties.
Food processing processes related to conventional BPs production include cooking, ripening, fermentation and germination. In principle, the processing involves protease enzymes, e.g., chymotrypsin, trypsin, papain, thermolysin, and others) [151], either in the form of free or immobilised enzymes. For food processing by fermentation, protease enzymes derived from microbes are used in the process, while for germination, the enzymes are from growing seeds. Production of BPs increased by regulating the types of enzymes, microbes used, and germination time. Combining these processes (enzymatic process followed by fermentation, or vice versa) will increase the production of BPs so that it is more optimal [152]. The conventional production of the BPs product was a low amount and purity, making it less effective for the industrial scale [153]. So this conventional method for producing BPs does not necessarily involve a separation and purification process, but the production of functional foods containing healthy BPs in the form of fermented food products [153].
The process technology used to produce functional or nutraceutical food will affect the functional, nutritional and biological properties of the protein in the food. Therefore, several things to pay attention to, namely: (1) the effect of using a thermal (or non-thermal) process on the components of the food produced, including its effect on its functional properties and preservation capabilities; (2) available extraction processes and formulations and their optimization; (3) innovative and sustainable applications that can be developed [127]. In addition, consideration of the choice of processing technology must also be based on the desired nutritional function and appearance and sensory properties (such as colour, texture, and taste in the mouth) to be attractive to consumers [154]. Thermal processes can encourage non-enzymatic Maillard reactions between amino groups and reducing sugars [155]. This process will produce colour, sensory properties that affect consumer acceptance and reduce the activity of BPs [155, 156]. The use of thermal processes (e.g. boiling, cooking, blanching, frying, and sterilising) for softening cell walls and inactivate microorganisms and enzymes to make the shelf life longer [127]. The development of non-thermal processes has several weaknesses; for example, the use of nanofiltration membranes requires energy [157]. Freeze-drying, encapsulation, and solvent extraction techniques are costly. To overcome this limitation, food technology experts must develop new alternative technologies (technology that can maintain bio-accessibility, stability, bio-availability and bio-activity of active components). Including BPs, processed food ingredients and the form of pure isolates (capsules or nanocapsules).
The production of BPs has become more accessible, faster, and more effective with the development of science and technology. Production of BPs on an industrial scale usually uses an enzyme hydrolysis process. So the BPs production process uses computer equipment and database search algorithms to predict target peptides and their properties. By selecting the correct protease enzyme through the database, it is possible to select the protein-enzyme combination, in-silico hydrolysis, and the nature of the peptide to be produced [152, 153, 158]. This in-silico hydrolysis method is a functional and widely practised approach for producing legume BPs (Table 3).
The legume or various food peptides resulting from enzymatic hydrolysis was then fractionated and purified using a combination of various chromatographic techniques [158, 159, 160]. Isoelectric focusing and ultrafiltration are separate macromolecular compounds (such as protein and pectin). Meanwhile, extraction techniques use solvents or supercritical solutions to isolate small molecule bioactive compounds such as antioxidants [157, 161, 162]. This extraction technique, combined with thermal technology (e.g. pasteurisation or spray drying), has been applied to functional foods. This conventional food processing technology is well documented and well established, but its application for the isolation of BPs still needs development and improvement.
The weakness of current technology is that there is still a need for studies on product safety for health. For example, advanced technologies such as cold plasma, nanotechnology, ultrasound, and others, are thought to affect advanced lipid oxidation processes and cause cell tissue damage. For this reason, the effect of this advanced technology on the safety and health of the food components produced needs to be studied to obtain a complete understanding. In this case, it is necessary to adapt the product and technology to the desired functional properties of the active ingredient. For example, modification or interaction with other macronutrients (e.g. dietary fibre) can increase the bio-availability of bioactive compounds [163].
On the other hand, encapsulation technology using legume protein ingredients as a material is also a technique for providing chemical compounds found naturally in plants and other nutraceutical compounds (such as vitamins, minerals, BPs, or others). Thus this encapsulation allowing these compounds (including BPs) to enter the body and undergo release and degradation by enzymes digestion [164]. Other technologies used to protect the active ingredients or nutraceuticals (such as BPs and others) are encapsulation, edible films and coatings, and vacuum impregnation. One may be promising is nutrigenomics, where the active ingredients are given to individuals on a Taylor-made basis according to the genetic characteristics of each individual [165].
Although several researchers have evaluated and characterised BPs that BPs isolated from food have potential bioactive activity and therapeutic functions, and have high bio-availability (bio-accessibility) (due to the support of excellent and modern processing technology), however, all of them can only have a positive impact on human health when combined with healthy living habits [4].
Legumes have various biological activities that are good for body health, such as antihypertensive, anti-diabetic, anti-cancer, antioxidant, and others, but legumes also contain anti-nutritional compounds. Food processing is an effective process to remove anti-nutritional compounds and, at the same time, can produce BP compounds that are healthy for the body. Although the number of active components in food is abundant, it is not necessarily able to prevent disease because it is very dependent on the amount available to function in target organs or tissues. One of the contributing factors is the BPs enzyme in holding the action while in the digestive tract. Some legumes showed that hydrolysis by these enzymes increased their bio-accessibility and bio-availability in the digestive tract of rats (in antihypertensive testing). Due to the diverse nature of BP, it is necessary to develop technology that is following the desired functional properties of BP, for example, to protect it so that it is stable while passing through the digestive tract using microencapsulation, edible film and coating technology. Further research still needs to be developed related to the study of safety separation technology for the products produced. From the excellent stability and bioavailability of BPs from legumes, it is likely to be more promising to develop alternative healthy functional food products containing BPs and sensory properties that attract consumers.
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',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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The toxic and allergic reactions of synthetic dyes are compelling the people to think about natural dyes. Natural dyes are renewable source of colouring materials. Besides textiles it has application in colouration of foods, medicine and in handicraft items. Though natural dyes are ecofriendly, protective to skin and pleasing colour to eyes, they are having very poor bonding with textile fibre materials, which necessitate mordanting with metallic mordants, some of which are not eco friendly, for fixation of natural dyes on textile fibres. So the supremacy of natural dyes is somewhat subdued. This necessitates newer research on application of natural dyes on different natural fibres for completely eco friendly textiles. The fundamentals of natural dyes chemistry and some of the important research work are therefore discussed in this review article.",book:{id:"9203",slug:"chemistry-and-technology-of-natural-and-synthetic-dyes-and-pigments",title:"Chemistry and Technology of Natural and Synthetic Dyes and Pigments",fullTitle:"Chemistry and Technology of Natural and Synthetic Dyes and Pigments"},signatures:"Virendra Kumar Gupta",authors:[{id:"305259",title:"Dr.",name:"Virendra",middleName:null,surname:"Kumar Gupta",slug:"virendra-kumar-gupta",fullName:"Virendra Kumar Gupta"}]},{id:"49647",title:"Fiber Selection for the Production of Nonwovens",slug:"fiber-selection-for-the-production-of-nonwovens",totalDownloads:10512,totalCrossrefCites:9,totalDimensionsCites:17,abstract:"The most significant feature of nonwoven fabric is made directly from fibers in a continuous production line. While manufacturing nonwovens, some conventional textile operations, such as carding, drawing, roving, spinning, weaving or knitting, are partially or completely eliminated. For this reason the choice of fiber is very important for nonwoven manufacturers. The commonly used fibers include natural fibers (cotton, jute, flax, wool), synthetic fibers (polyester (PES), polypropylene (PP), polyamide, rayon), special fibers (glass, carbon, nanofiber, bi-component, superabsorbent fibers). Raw materials have not only delivered significant product improvements but also benefited people using these products by providing hygiene and comfort.",book:{id:"5062",slug:"non-woven-fabrics",title:"Non-woven Fabrics",fullTitle:"Non-woven Fabrics"},signatures:"Nazan Avcioglu Kalebek and Osman Babaarslan",authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",slug:"osman-babaarslan",fullName:"Osman Babaarslan"},{id:"175829",title:"Dr.",name:"Nazan",middleName:null,surname:"Kalebek",slug:"nazan-kalebek",fullName:"Nazan Kalebek"}]},{id:"41409",title:"Surface Modification Methods for Improving the Dyeability of Textile Fabrics",slug:"surface-modification-methods-for-improving-the-dyeability-of-textile-fabrics",totalDownloads:7038,totalCrossrefCites:13,totalDimensionsCites:36,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Sheila Shahidi, Jakub Wiener and Mahmood Ghoranneviss",authors:[{id:"58854",title:"Dr.",name:null,middleName:null,surname:"Shahidi",slug:"shahidi",fullName:"Shahidi"}]}],onlineFirstChaptersFilter:{topicId:"296",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters: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:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. 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Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}}]}},subseries:{item:{id:"28",type:"subseries",title:"Animal Reproductive Biology and Technology",keywords:"Animal Reproduction, Artificial Insemination, Embryos, Cryopreservation, Conservation, Breeding, Epigenetics",scope:"The advances of knowledge on animal reproductive biology and technologies revolutionized livestock production. Artificial insemination, for example, was the first technology applied on a large scale, initially in dairy cattle and afterward applied to other species. Nowadays, embryo production and transfer are used commercially along with other technologies to modulate epigenetic regulation. Gene editing is also emerging as an innovative tool. This topic will discuss the potential use of these techniques, novel strategies, and lines of research in progress in the fields mentioned above.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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