Main studies on therapeutic delivery with MNDs. Adapted from [56].
\\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!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 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 252 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!
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"2187",leadTitle:null,fullTitle:"Nuclear Power - Practical Aspects",title:"Nuclear Power",subtitle:"Practical Aspects",reviewType:"peer-reviewed",abstract:"The serious challenge facing the world today, in obtaining enough energy for growing population and in controlling the carbon emission caused by fossil fuel use, calls for nuclear energy as an alternative power source. This book presents research work and technical experience from several power plants and research institutions around the world from practical prospective. This book intends to provide useful information for scientists and those in technical fields in several areas in nuclear power plants including: nuclear systems protection, design and modelling of critical parameters in nuclear power plants, thermalhydraulic analysis, nuclear waste management and safety and reliability assessment.",isbn:null,printIsbn:"978-953-51-0778-1",pdfIsbn:"978-953-51-6247-6",doi:"10.5772/2580",price:119,priceEur:129,priceUsd:155,slug:"nuclear-power-practical-aspects",numberOfPages:248,isOpenForSubmission:!1,isInWos:1,hash:"d1dd542ff5cd5c2b788aac5553050b9b",bookSignature:"Wael Ahmed",publishedDate:"October 10th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2187.jpg",numberOfDownloads:20083,numberOfWosCitations:18,numberOfCrossrefCitations:10,numberOfDimensionsCitations:17,hasAltmetrics:0,numberOfTotalCitations:45,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 7th 2011",dateEndSecondStepPublish:"January 11th 2012",dateEndThirdStepPublish:"April 16th 2012",dateEndFourthStepPublish:"July 15th 2012",dateEndFifthStepPublish:"August 14th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"29906",title:"Dr.",name:"Wael",middleName:"H.",surname:"Ahmed",slug:"wael-ahmed",fullName:"Wael Ahmed",profilePictureURL:"https://mts.intechopen.com/storage/users/29906/images/3257_n.jpg",biography:"Dr. Wael Ahmed is currently an Assistant Professor of Mechanical Engineering at KFUPM, Dhahran, Saudi Arabia. He finished his B.Sc. and M.Sc. from Alexandria University in Egypt and his Ph.D. degree in Mechanical Engineering from McMaster University, in Canada in 2005. He worked for the R&D division of Atomic of Energy of Canada Ltd. from 2005-2008. Before joining KFUPM in 2009, he worked as senior analyst at Nuclear Safety Solutions in providing technical support to Nuclear Power Plant in the area of plant life assessment. Dr. Ahmed carried out multi-million dollars research and project work to Ontario Power Generation, Hydro-Quebec, Gas-Tops, Bruce Power and Pratt& Whitney Canada in the areas of Flow Accelerated Corrosion and multiphase flow.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"King Fahd University of Petroleum and Minerals",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"769",title:"Power Engineering",slug:"engineering-energy-engineering-power-engineering"}],chapters:[{id:"39782",title:"Power System Protection Design for NPP",doi:"10.5772/50557",slug:"power-system-protection-design-for-npp",totalDownloads:2558,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Chang-Hsing Lee and Shi-Lin Chen",downloadPdfUrl:"/chapter/pdf-download/39782",previewPdfUrl:"/chapter/pdf-preview/39782",authors:[{id:"141862",title:"Dr.",name:"Chang-Hsing",surname:"Lee",slug:"chang-hsing-lee",fullName:"Chang-Hsing Lee"},{id:"149886",title:"Prof.",name:"Shi-Lin",surname:"Chen",slug:"shi-lin-chen",fullName:"Shi-Lin Chen"}],corrections:null},{id:"39783",title:"Reliability of Passive Systems in Nuclear Power Plants",doi:"10.5772/47862",slug:"reliability-of-passive-systems-in-nuclear-power-plants",totalDownloads:2874,totalCrossrefCites:3,totalDimensionsCites:2,signatures:"Luciano Burgazzi",downloadPdfUrl:"/chapter/pdf-download/39783",previewPdfUrl:"/chapter/pdf-preview/39783",authors:[{id:"144551",title:"Dr.",name:"Luciano",surname:"Burgazzi",slug:"luciano-burgazzi",fullName:"Luciano Burgazzi"}],corrections:null},{id:"39836",title:"Geological Disposal of Nuclear Waste: Fate and Transport of Radioactive Materials",doi:"10.5772/50391",slug:"geological-disposal-of-nuclear-waste-fate-and-transport-of-radioactive-materials",totalDownloads:1886,totalCrossrefCites:2,totalDimensionsCites:2,signatures:"Prabhakar Sharma",downloadPdfUrl:"/chapter/pdf-download/39836",previewPdfUrl:"/chapter/pdf-preview/39836",authors:[{id:"141480",title:"Dr.",name:"Prabhakar",surname:"Sharma",slug:"prabhakar-sharma",fullName:"Prabhakar Sharma"}],corrections:null},{id:"39781",title:"Seismic Safety Analysis and Upgrading of Operating Nuclear Power Plants",doi:"10.5772/51368",slug:"seismic-safety-analysis-and-upgrading-of-operating-nuclear-power-plants",totalDownloads:2784,totalCrossrefCites:2,totalDimensionsCites:3,signatures:"Tamás János Katona",downloadPdfUrl:"/chapter/pdf-download/39781",previewPdfUrl:"/chapter/pdf-preview/39781",authors:[{id:"10716",title:"Dr.",name:"Tamás János",surname:"Katona",slug:"tamas-janos-katona",fullName:"Tamás János Katona"}],corrections:null},{id:"39785",title:"Probabilistic Assessment of Nuclear Power Plant Protection Against External Explosions",doi:"10.5772/51492",slug:"probabilistic-assessment-of-nuclear-power-plant-protection-against-external-explosions",totalDownloads:1266,totalCrossrefCites:1,totalDimensionsCites:4,signatures:"Heinz Peter Berg and Jan Hauschild",downloadPdfUrl:"/chapter/pdf-download/39785",previewPdfUrl:"/chapter/pdf-preview/39785",authors:[{id:"10632",title:"Dr.",name:"Heinz-Peter",surname:"Berg",slug:"heinz-peter-berg",fullName:"Heinz-Peter Berg"},{id:"144136",title:"Dr.",name:"Jan",surname:"Hauschild",slug:"jan-hauschild",fullName:"Jan Hauschild"}],corrections:null},{id:"39784",title:"Flow Accelerated Corrosion in Nuclear Power Plants",doi:"10.5772/51346",slug:"flow-accelerated-corrosion-in-nuclear-power-plants",totalDownloads:6481,totalCrossrefCites:2,totalDimensionsCites:6,signatures:"Wael H. Ahmed",downloadPdfUrl:"/chapter/pdf-download/39784",previewPdfUrl:"/chapter/pdf-preview/39784",authors:[{id:"29906",title:"Dr.",name:"Wael",surname:"Ahmed",slug:"wael-ahmed",fullName:"Wael Ahmed"}],corrections:null},{id:"39823",title:"Thermal Reactors with High Reproduction of Fission Materials",doi:"10.5772/51599",slug:"thermal-reactors-with-high-reproduction-of-fission-materials",totalDownloads:1406,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Vladimir M. Kotov",downloadPdfUrl:"/chapter/pdf-download/39823",previewPdfUrl:"/chapter/pdf-preview/39823",authors:[{id:"143828",title:"Mr.",name:"Vladimir",surname:"Kotov",slug:"vladimir-kotov",fullName:"Vladimir Kotov"}],corrections:null},{id:"39990",title:"On an Analytical Model for the Radioactive Contaminant Release in the Atmosphere from Nuclear Power Plants",doi:"10.5772/51525",slug:"on-an-analytical-model-for-the-radioactive-contaminant-release-in-the-atmosphere-from-nuclear-power-",totalDownloads:834,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Marco Túllio Vilhena, Bardo Bodmann, Umberto Rizza and Daniela Buske",downloadPdfUrl:"/chapter/pdf-download/39990",previewPdfUrl:"/chapter/pdf-preview/39990",authors:[{id:"10869",title:"Prof.",name:"Marco Tullio",surname:"Vilhena",slug:"marco-tullio-vilhena",fullName:"Marco Tullio Vilhena"},{id:"49001",title:"Prof.",name:"Bardo",surname:"Bodmann",slug:"bardo-bodmann",fullName:"Bardo Bodmann"},{id:"144993",title:"Dr.",name:"Umberto",surname:"Rizza",slug:"umberto-rizza",fullName:"Umberto Rizza"},{id:"144995",title:"Dr.",name:"Daniela",surname:"Buske",slug:"daniela-buske",fullName:"Daniela Buske"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"1073",title:"Wireless Power Transfer",subtitle:"Principles and Engineering Explorations",isOpenForSubmission:!1,hash:"539623d2f9a1dca563421e451940e4e1",slug:"wireless-power-transfer-principles-and-engineering-explorations",bookSignature:"Ki Young Kim",coverURL:"https://cdn.intechopen.com/books/images_new/1073.jpg",editedByType:"Edited by",editors:[{id:"12009",title:"Dr.",name:"Ki Young",surname:"Kim",slug:"ki-young-kim",fullName:"Ki Young Kim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3177",title:"Wind Power",subtitle:null,isOpenForSubmission:!1,hash:"9a5f2db2003e1dfb3beb19541b2faf87",slug:"wind-power",bookSignature:"S M Muyeen",coverURL:"https://cdn.intechopen.com/books/images_new/3177.jpg",editedByType:"Edited by",editors:[{id:"122699",title:"Prof.",name:"S. M.",surname:"Muyeen",slug:"s.-m.-muyeen",fullName:"S. M. Muyeen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3589",title:"ICT - Energy - Concepts Towards Zero",subtitle:"Power Information and Communication Technology",isOpenForSubmission:!1,hash:"52d111bb721e0d749c1cee6c8b6d8ab8",slug:"ict-energy-concepts-towards-zero-power-information-and-communication-technology",bookSignature:"Giorgos Fagas, Luca Gammaitoni, Douglas Paul and Gabriel Abadal Berini",coverURL:"https://cdn.intechopen.com/books/images_new/3589.jpg",editedByType:"Edited by",editors:[{id:"168209",title:"Dr.",name:"Giorgos",surname:"Fagas",slug:"giorgos-fagas",fullName:"Giorgos Fagas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3660",title:"Nuclear Power",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"nuclear-power",bookSignature:"Pavel Tsvetkov",coverURL:"https://cdn.intechopen.com/books/images_new/3660.jpg",editedByType:"Edited by",editors:[{id:"10023",title:"Dr.",name:"Pavel",surname:"Tsvetkov",slug:"pavel-tsvetkov",fullName:"Pavel Tsvetkov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3724",title:"Distributed Generation",subtitle:null,isOpenForSubmission:!1,hash:"9383c05ece5ed76feff7645f261830ba",slug:"distributed-generation",bookSignature:"D N Gaonkar",coverURL:"https://cdn.intechopen.com/books/images_new/3724.jpg",editedByType:"Edited by",editors:[{id:"112984",title:"Dr.",name:"Dattatraya",surname:"Gaonkar",slug:"dattatraya-gaonkar",fullName:"Dattatraya Gaonkar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"62",title:"Power Quality",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"power-quality",bookSignature:"Andreas Eberhard",coverURL:"https://cdn.intechopen.com/books/images_new/62.jpg",editedByType:"Edited by",editors:[{id:"18782",title:"Mr.",name:"Andreas",surname:"Eberhard",slug:"andreas-eberhard",fullName:"Andreas Eberhard"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5413",title:"Thermoelectrics for Power Generation",subtitle:"A Look at Trends in the Technology",isOpenForSubmission:!1,hash:"d81a819e53a5ff35501b9876d5f6b1ab",slug:"thermoelectrics-for-power-generation-a-look-at-trends-in-the-technology",bookSignature:"Sergey Skipidarov and Mikhail Nikitin",coverURL:"https://cdn.intechopen.com/books/images_new/5413.jpg",editedByType:"Edited by",editors:[{id:"16374",title:"Dr.",name:"Mikhail",surname:"Nikitin",slug:"mikhail-nikitin",fullName:"Mikhail Nikitin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3076",title:"Advances in Wind Power",subtitle:null,isOpenForSubmission:!1,hash:"7fd7c5d70cbc111f7a84a512c2189d48",slug:"advances-in-wind-power",bookSignature:"Rupp Carriveau",coverURL:"https://cdn.intechopen.com/books/images_new/3076.jpg",editedByType:"Edited by",editors:[{id:"22234",title:"Dr.",name:"Rupp",surname:"Carriveau",slug:"rupp-carriveau",fullName:"Rupp Carriveau"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"477",title:"Nuclear Power",subtitle:"Control, Reliability and Human Factors",isOpenForSubmission:!1,hash:null,slug:"nuclear-power-control-reliability-and-human-factors",bookSignature:"Pavel Tsvetkov",coverURL:"https://cdn.intechopen.com/books/images_new/477.jpg",editedByType:"Edited by",editors:[{id:"10023",title:"Dr.",name:"Pavel",surname:"Tsvetkov",slug:"pavel-tsvetkov",fullName:"Pavel Tsvetkov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3073",title:"Power Quality Issues",subtitle:null,isOpenForSubmission:!1,hash:"41be446d0a7e208798819a2e31c44960",slug:"power-quality-issues",bookSignature:"Ahmed Zobaa",coverURL:"https://cdn.intechopen.com/books/images_new/3073.jpg",editedByType:"Edited by",editors:[{id:"39249",title:"Dr.",name:"Ahmed F.",surname:"Zobaa",slug:"ahmed-f.-zobaa",fullName:"Ahmed F. Zobaa"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"66063",slug:"corrigendum-to-introductory-chapter-historical-perspective-and-brief-overview-of-insulin",title:"Corrigendum to: Introductory Chapter: Historical Perspective and Brief Overview of Insulin",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/66063.pdf",downloadPdfUrl:"/chapter/pdf-download/66063",previewPdfUrl:"/chapter/pdf-preview/66063",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/66063",risUrl:"/chapter/ris/66063",chapter:{id:"63640",slug:"introductory-chapter-historical-perspective-and-brief-overview-of-insulin",signatures:"Gaffar Sarwar Zaman",dateSubmitted:"June 29th 2018",dateReviewed:"August 28th 2018",datePrePublished:"November 5th 2018",datePublished:"February 6th 2019",book:{id:"6675",title:"Ultimate Guide to Insulin",subtitle:null,fullTitle:"Ultimate Guide to Insulin",slug:"ultimate-guide-to-insulin",publishedDate:"February 6th 2019",bookSignature:"Gaffar Zaman",coverURL:"https://cdn.intechopen.com/books/images_new/6675.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",slug:"gaffar-sarwar-zaman",fullName:"Gaffar Sarwar Zaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",fullName:"Gaffar Sarwar Zaman",slug:"gaffar-sarwar-zaman",email:"gffrzaman@gmail.com",position:null,institution:{name:"King Khalid University",institutionURL:null,country:{name:"Saudi Arabia"}}}]}},chapter:{id:"63640",slug:"introductory-chapter-historical-perspective-and-brief-overview-of-insulin",signatures:"Gaffar Sarwar Zaman",dateSubmitted:"June 29th 2018",dateReviewed:"August 28th 2018",datePrePublished:"November 5th 2018",datePublished:"February 6th 2019",book:{id:"6675",title:"Ultimate Guide to Insulin",subtitle:null,fullTitle:"Ultimate Guide to Insulin",slug:"ultimate-guide-to-insulin",publishedDate:"February 6th 2019",bookSignature:"Gaffar Zaman",coverURL:"https://cdn.intechopen.com/books/images_new/6675.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",slug:"gaffar-sarwar-zaman",fullName:"Gaffar Sarwar Zaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",fullName:"Gaffar Sarwar Zaman",slug:"gaffar-sarwar-zaman",email:"gffrzaman@gmail.com",position:null,institution:{name:"King Khalid University",institutionURL:null,country:{name:"Saudi Arabia"}}}]},book:{id:"6675",title:"Ultimate Guide to Insulin",subtitle:null,fullTitle:"Ultimate Guide to Insulin",slug:"ultimate-guide-to-insulin",publishedDate:"February 6th 2019",bookSignature:"Gaffar Zaman",coverURL:"https://cdn.intechopen.com/books/images_new/6675.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",slug:"gaffar-sarwar-zaman",fullName:"Gaffar Sarwar Zaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10918",leadTitle:null,title:"Digital Economy",subtitle:null,reviewType:"peer-reviewed",abstract:"This book will be a self-contained collection of scholarly papers targeting an audience of practicing researchers, academics, PhD students and other scientists. The contents of the book will be written by multiple authors and edited by experts in the field.",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"dbdfd9caf5c4b0038ff4446c7bc6a681",bookSignature:"",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10918.jpg",keywords:null,numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 25th 2020",dateEndSecondStepPublish:"December 16th 2020",dateEndThirdStepPublish:"February 14th 2021",dateEndFourthStepPublish:"May 5th 2021",dateEndFifthStepPublish:"July 4th 2021",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:1,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"7",title:"Business, Management and Economics",slug:"business-management-and-economics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited 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"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"45224",title:"Three-Dimensional Lithography Using Combination of Nanoscale Processing and Wet Chemical Etching",doi:"10.5772/56354",slug:"three-dimensional-lithography-using-combination-of-nanoscale-processing-and-wet-chemical-etching",body:'Nanofabrication technology is an important field of research, and numerous attempts have been made to improve this technology in recent years. This technology is demanded in various industrial fields such as electronic, photonic, and biomedical engineering to miniaturize machine components. Through miniaturization, the integration and parallelization of components in a machine device are possible, leading to reductions in dead space and fabrication cost. A high-performance device can be fabricated using the changes in physicochemical behavior due to scaling effects; the resonance frequency, thermal response, and chemical reaction all increase with miniaturization. These characteristics are particularly effective in devices such as sensors and reactors. Additionally, Newton’s laws of motion do not hold for distances less than 10 nm owing to increased quantum mechanical effects, so that certain types of functions only occur in miniaturized devices. Devices that maximize these effects include microelectromechanical systems and nanoelectromechanical systems, which consist of micro/nanometer-scale mechanical components integrated on a silicon surface.
The conventional fabrication methods of these components are based on photolithography [1], which is a fabrication method used for semiconductor devices. This technique is suitable for mass producing micro/nanostructures because it is a high-throughput fabrication process. It was developed based on Moore’s law [2], and it can fabricate sub-100-nm patterns by using deep ultraviolet light with wavelengths of 248 nm and 193 nm. Other major approaches include reactive ion etching [3] and LIGA (lithographie, galvanoformung, abformung) [4], which are mainly used to fabricate high-aspect-ratio structures. However, these fabrication processes use a photomask, which is a high-cost and time-consuming step. Layering and etching techniques are used to fabricate complex structures, but it is difficult to fabricate complex three-dimensional structures. However, several successful attempts have been made to fabricate nano/micrometer-scale structures using scanning probe microscopy (SPM), focused ion beam (FIB), and electron beam (EB) lithography. Though these methods are effective for fabricating nanometer-scale structures, time-consuming steps are necessary for fabricating sub-micrometer to micrometer-scale structures. Higher and wider structures can be fabricated by taking advantage of the combination of the high resolution of these lithographic techniques and the high-speed material removal of wet chemical etching. Three-dimensional structures can also be fabricated by using this combination of lithography and etching.
Three processing techniques are introduced for three-dimensional fabrication using a combination of nanoscale processing and wet chemical etching. The first is tribo-nanolithography (TNL), which forms an amorphous silicon phase on a silicon substrate by using direct machining, similar to mechanical scratching. The second technique is FIB irradiation, which forms an amorphous phase on a silicon substrate by irradiating it with accelerated ions. The last is EB irradiation, which causes the formation of a thin hydrocarbon layer that has an etch resistance. The etch rate of the processing layer is different from the original material surface, enabling structures to be fabricated after the etching. Additionally, three-dimensional structures can be fabricated using these techniques. The fundamental characteristics and possible applications of these methods are described in the following sections.
SPM, which includes scanning tunneling microscopy (STM) [5], atomic force microscopy (AFM) [6], and scanning near-field optical microscopy (SNOM) [7], was developed to observe surface characteristics via detecting interactions between a probe and solid materials. The most used instruments in the SPM family are STM and AFM. STM is used to measure the surface topography with atomic resolution by detecting the tunneling current, and AFM measures the topography by detecting minute forces between the probe and the sample. These instruments have a probe and a scanning stage, which means they can be used as a micro tool with a precise stage, similar to a machine tool. Therefore, several micro/nanostructuring technologies arose after the development of these instruments; this technique enabled researchers to manipulate even single atoms [8]. Thus, an SPM can be used as not only a measuring tool but also as a nanostructuring tool, making it appropriate for nanoscale lithography.
SPM lithography can be used to fabricate nanoscale structures by various methods such as electrochemical oxidation [9–11], material transfer [12–14], mechanical removal [15–19] and thermal reaction [21, 22]. This technique is effective for fabricating nanometer-scale structures. However, for fabricating larger structures, time-consuming steps are necessary. The chemical properties of the patterned area change, although the mechanism is different for each method. The patterned area can then be used as an etching mask or it can be selectively etched, and micro/nanometer structures can then be fabricated [9–11, 14, 19]. SPM lithography is used only for the patterning; the structures are fabricated with subsequent etching, which can remove a large amount of material at a time. Thus, SPM lithography with etching is suitable for fabricating structures with a height over several tens of nanometers, whereas SPM lithography alone can only be used for structures that are a few nanometers high. Additionally, three-dimensional structures can be fabricated by controlling the etching mask. Herein we describe a method of three-dimensional fabrication using TNL [19, 22–28] with wet chemical etching.
TNL uses AFM as a machine tool for nanopatterning, which enables one to measure the machining forces as well as the machine materials. The technique can be used to machine a material surface with large normal loads by employing a specially designed diamond tip cantilever. The machining setup, based on AFM, is schematically shown in Figure 1(a). The machining forces can be measured from the deflection and torsion of the cantilever, which are both detected by a four-segment photodetector. The normal load is kept constant by a feedback control from a piezo scanner. In the machining process, the specially designed cantilever [18, 29, 30] shown in Figure 1(b) is installed in the system instead of conventional Si3N4 or silicon cantilevers. This cantilever has a diamond tip attached to a silicon lever, which has a very high stiffness of more than 1000 times that of conventional cantilevers.
a) Schematic diagram of the experimental setup for TNL based on AFM. (b) SEM image of the cantilever for machining. Reprinted with permission from [29]. Copyright 2006, ASME.
The TNL method forms a modified area on the surface of the silicon substrate via a direct nanomachining method, similar to mechanical scratching. The machining characteristics of the cantilever change significantly owing to the shape of the diamond tip. Figure 2 shows a scanning electron microscopy (SEM) image of cutting tips with different radii. Figure 3 shows AFM topography images of silicon surfaces machined with these cantilevers [30]. When a sharper tip is used, the machined surface is removed and a concave pattern is fabricated, as shown in Figure 3(a) [29, 30]. In this case, continuous cutting chips are formed because the cutting was conducted in a ductile mode owing to the small cutting depth. A dull tip tends not to remove material from the machined area, as shown in Figure 3(b), but instead introduces a high-pressure region to the substrate. Additionally, a 1–2 nm high protuberance was formed, induced by the volume expansion of the machined area [19, 30]. A dull tip is used in the TNL method because it is more suitable for fabricating precise low-linewidth structures [23].
SEM image of diamond tips with (a) sharp and (b) dull cutting edges.
AFM topography images of machined areas. Silicon surfaces were machined with (a) sharp and (b) dull cutting edges at normal loads of 331 µN and 340 µN, respectively.
The fabrication of a structure using a combination of TNL and wet chemical etching is shown in Figure 4 [19]. Figure 4(a) shows an AFM image of the topography of a machined area (15 × 7.5 µm2 area) prepared using TNL at a normal load of 310 µN and a scanning pitch of 59 nm. The minute protuberance, which is only 1–2 nm high, was formed on the machined area. Figure 4(b) shows an AFM topography image of the same area after etching in a 10 mass% potassium hydroxide (KOH) for 5 min. The machined area was able to resist etching in KOH, whereas the nonmachined area was etched. Thus, a protruding structure with a height of 110 nm was fabricated on the machined area. However, this machined area could also be selectively dissolved in hydrogen fluoride (HF), with the nonmachined silicon surface being barely etched [1]. In this way, a concave structure with a depth of several nanometers to several tens of nanometers could be fabricated from the machined area.
Structure fabrication using a combination of TNL and wet chemical etching. (a) AFM topography image of the machined area (15 × 7.5 µm2 area) prepared using TNL at a normal load of 310 µN. (b) AFM topography image of the same area after etching in 10 mass% KOH for 5 min. Reprinted with permission from [19]. Copyright 2005, IOP Publishing.
The TNL-induced etch resistance of the machined area is due to the formation of an amorphous phase. Cross-sectional transmission electron microscopy (TEM) images and nano-electron diffraction (nano-ED) patterns of the machined areas prepared by TNL are shown in Figure 5 [19]. Figure 5(a) shows a cross-sectional TEM image of the silicon substrate after machining a single line at a normal load of 350 µN. This image shows that an affected layer measuring 100 nm wide and 15 nm deep was formed. This indicates that the volume expansion of the machined area shown in Figure 4(a) resulted from this layer. The nano-ED pattern of the affected layer in Figure 5(c) shows a diffuse ring pattern, whereas that of the nonmachined area in Figure 5(d) shows a silicon crystal pattern, meaning the machined area was converted to an amorphous phase. Figure 5(b) shows cross-sectional TEM images of the machined area prepared at a scanning pitch of 50 nm. The amorphous phase was thicker than that of a machined single line, and the thickness was observed to be 20 nm. Furthermore, a concave-convex pattern of the silicon crystal structure, which has the same pitch as the scanning pitch, is formed under the amorphous phase. Secondary ion mass spectrometry and Auger electron spectroscopy analyses have shown that the amorphous phase consists entirely of silicon. Therefore, the etch stop effect of the machined area results from the formation of the amorphous phase, rather than from the formation of a chemical compound such as silicon oxide or silicon hydroxide. The TNL-induced amorphous phase was also formed via the removal method, shown in Figure 3(a), by applying the sharp tip with a higher normal load [20]. In this case, a thicker amorphous phase was formed under the machined area as well as large dislocations. The dislocations induced a KOH etching enhancement rather than an etch stop effect. Therefore, in the material removal method, a convex or concave structure can be fabricated by the etching in KOH from the etch stop and etching enhancement effects, which is decided by the concentration of KOH.
The phase transition of the silicon from crystalline to amorphous is due to the high pressure induced by the TNL. During machining, a significantly high pressure is introduced at the contact region of the probe and the silicon substrate, which creates the amorphous silicon phase. Machining-induced phase transitions have been observed during various types of machining at nano to submicron scales, such as turning [31, 32], grinding [33], indentation [34, 35], and scratching [36, 37]. Silicon, which has a diamond crystal structure, converts to a β-Sn structure at a pressure of approximately 12 GPa, and then converts to an amorphous phase during the pressure release process [37]. This is the mechanism by which the area machined by TNL is converted to an amorphous phase.
Bright field cross-sectional TEM image of machined area prepared by TNL. (a) Machined area of a single line at a normal load of 350 µN. (b) Machined area prepared at a normal load of 350 µN with a scanning pitch of 50 nm. Nano-ED patterns of a machined area A in (c), and a nonmachined area B in (d). Reprinted with permission from [19]. Copyright 2005, IOP Publishing.
The morphology of the amorphous phase depends on the machining-induced pressure, and therefore, it can be controlled by the machining conditions. Thus, the change in etch resistance of the amorphous phase can be used to fabricate a three-dimensional structure. The height dependence of the etch rate, the height of the protuberance, and the height of the structure on the normal load is shown in Figure 6 [27]. The silicon surface was machined at various normal loads and then etched in 10 mass% KOH for 10 min. The machined area protruded for normal loads less than 372 µN, whereas the machined area was removed and a concave structure was fabricated for normal loads greater than 372 µN. Therefore, the machining mode is divided into protuberance and removal regions, as shown in the figure. The etch rate of the machined area decreased and the structure height increased with increasing normal loading for the protuberance region. However, the etch rate was nearly constant in the removal region owing to the dislocations formed by the removal machining at higher normal loads. The dislocations enhanced the silicon etching in KOH [22]. Therefore, a constant etch rate at the removal region resulted from the interaction between the amorphous phase (etch stop effect) and dislocation (etching enhancement effect) formed by the machining. These results demonstrate that the etch resistance can be controlled by the normal load in the protuberance region, whereas it is constant in the removal region. The etch resistance can also be increased by other machining conditions, such as the overlap ratio and number of times the area is machined [23].
Etch rate of the machined area when the silicon was machined at various normal loads and then etched in 10 mass% KOH for 10 min.
The change in the etch rate of the machined area owing to the machining conditions is caused by the morphology of the amorphous phase. To study this, the morphology of the amorphous phase is measured by etching in HF. Figure 7 shows a cross-sectional TEM image of the machined area prepared at a normal load of 350 µN and a scanning pitch of 50 nm, the same conditions as Figure 5(b), after etching in 25 mass% HF for 10 min [27]. The amorphous phase formed in the machined area was removed, and the concave-convex pattern of the silicon crystal phase remained. The single-crystal silicon surface was scarcely etched in HF [1]. Therefore, the concave structure shown in Figure 7 resulted from the selective removal of the TNL-induced amorphous phase by etching in HF.
Figure 8 shows the thickness of the amorphous phase for various normal loads [27]. The maximum height of protuberance after machining was observed at a normal load of 278 µN. After etching, the depth of the machined area increased with increasing normal load. The amorphous phase was formed by the high-pressure phase transition induced by the TNL [19], and increased in thickness with increasing normal load. Hence, for higher normal loads, a deeper region tended to be transformed to the amorphous phase owing to the high pressure, forming a thicker amorphous phase and resulting in a higher etch resistance against KOH. The thickness of the amorphous phase is directly correlated to the changes in the etch resistance of the machined area. Alternatively, changes in the etch resistance against KOH due to the scanning pitch and the number of times the area is machined result from the density of the amorphous phase rather than its thickness [27].
Bright-field cross-sectional TEM image of the machined area after etching in 25 mass% HF for 10 min. The silicon was machined at a normal load of 350 µN and a scanning pitch of 50 nm.
Changes in the thickness of the amorphous phase after the silicon was machined at various normal loads and etched in 25 mass% HF for 10 min.
Figure 9 shows three-dimensional structures with uniform height fabricated by TNL and wet chemical etching. Figures 9(a) shows a “Toyama Prefecture” (located in Japan) pattern. Structures that are several tens to hundreds of nanometers high can be fabricated using this simple method by machining under constant machining conditions [19]. Figure 9(b) shows a structure with a high aspect ratio fabricated on a (110)-oriented silicon surface. The silicon surface was machined along the <112> direction to take advantage of the anisotropic etching of silicon, and then etched in KOH [28]. This produced structures 150 nm wide and 800 nm high, with an aspect ratio of 5.3. Figure 10 shows a three-dimensional structure fabricated by exploiting the change in the etch resistance with the normal load [23]. The silicon surface was machined using five different normal loads in the range of 124 to 372 µN and protruded to a height of several nanometers after machining, as shown in Figure 10(a). After etching, a stepped structure with five different heights was produced, as shown in Figure 10(b).
This method can be used to fabricate three-dimensional structures with varying heights that cannot be fabricated via conventional photolithographic processes. A three-dimensional sloped structure can also be fabricated by machining while etching in KOH, owing to the simultaneous formation of an amorphous phase with etching [24, 25]. Therefore, this method is effective for various industrial fields in which three-dimensional structures are required.
Structures fabricated by TNL and wet chemical etching. (a) AFM topography image of a “Toyama Prefecture” pattern fabricated at a normal load of 350 µN followed by wet chemical etching in KOH for 1 min. (b) SEM image of a high-aspect-ratio structure. The (110)-oriented silicon surface was machined along the <112> direction and then etched in KOH for 12 min.
Stepped structure fabricated by TNL and wet chemical etching. (a) AFM topography image of a silicon surface machined using five different normal loads spanning the range of 124 to 372 µN. (b) The same area after etching in 10 mass% KOH for 10 min [27].
FIB is an instrument that irradiates ions focused over a range of a few nanometers to a few micrometers, accelerating them to an ion energy of 5 to 150 keV [38]. Using FIB, nanostructures can be fabricated by using the interactions of the irradiated ions with substrate atoms and/or introduced gases. The interaction causes sputtering [39–41], deposition [42–44], and implantation [45, 46] effects. Sputtering and deposition are used to fabricate nanometer-scale structures, whereas implantation is used to control the electrical properties of the material. FIB methods can be used to machine a sample surface to atomic scales and are thus suitable for fabricating structures that are a few tens of nanometers in size. The most used application of this method is the preparation of TEM samples, for which a thin sample is necessary.
A silicon surface irradiated with ion beams resists some etchants such as KOH [47–55], tetramethylammonium hydroxide [58], sodium hydroxide [50], and hydrazine [56, 57], so that protruding structures can be fabricated via etching. This phenomenon is not dependent on the species of the irradiated ions and has been reported after irradiating Ga [47–53], Si [49, 51, 54–56], Au [49], BF2 [56], Ni [57], and P [56, 58] ions. The “etch stop” effect of the ion-irradiated area is caused by the formation of an amorphous phase due to ion irradiation [55]. This method is effective for fabricating large structures because the ion irradiation time is significantly shorter than what is required for sputtering and deposition processes. A wet chemical etching process can be used to remove a large amount of material in a short amount of time. The height of the fabricated structure is uniform because the ion-irradiation-induced etching masks have sufficient etch resistance, similar to conventional photolithographic techniques. However, by controlling the etch resistance of the etching mask, the height can be controlled, and therefore, three-dimensional structures can be fabricated. Herein, a three-dimensional fabrication method using FIB irradiation and wet chemical etching [59–61] is described.
A fabrication method using a combination of FIB irradiation and wet chemical etching is shown in Figure 11 [59]. Figure 11(a) shows an AFM topography image of a silicon surface area after 30 keV Ga+ ion irradiation (5 × 5 µm2 area) at a dose of 13.0 µC/cm2. This dose value is significantly lower than that used for structure fabrication via sputtering. This image shows a minute protuberance of the irradiated area, which is only 1–2 nm in height. This phenomenon results from the formation of an amorphous phase induced by FIB irradiation, similar to the effect of TNL shown in Figure 4(a). Figure 11(b) shows an AFM topography image of the irradiated area after etching in 20 mass% KOH for 5 min. The irradiated area resists etching in KOH, whereas the nonirradiated area is etched, resulting in a protruding structure with a height of 169 nm. The etching characteristics of the irradiated area are different depending on the etchant species. Figure 11(c) shows an AFM topography image of the irradiated area after etching in 46 mass% HF for 20 min. The irradiated area is selectively etched in HF, whereas the nonirradiated area is scarcely etched [1]. Therefore, a concave structure with a depth of 33 nm is fabricated on the irradiated area. This result indicates that the shape of the structure (convex or concave) can be selected by using different etchants.
Etching characteristics of a FIB-irradiated area [59, 61]. (a) AFM topography image of a silicon surface after irradiation with 30 keV Ga+ ions at a dose of 13.0 µC/cm2. AFM topography image of an irradiated area (b) after etching in 20 mass% KOH for 5 min, and (c) after etching in 46 mass% HF for 60 min.
The difference in the etch resistance against KOH is caused by the thickness and density of the irradiation-induced amorphous phase. Figure 12 shows the cross-sectional TEM images and nano-ED patterns of 30 keV Ga+ ion-irradiated areas at different doses before and after etching in KOH. An amorphous phase formed in the irradiated area at lower doses, as indicated by the TEM and nano-ED images in Figures 12(a) and (e), respectively. The center of the amorphous phase was 20–30 nm deep, expanding to a depth of 70 nm. The amorphous phase was completely etched, forming a concave–convex pattern on the surface, as shown in Figure 12(b). A thicker and wider amorphous phase formed at a higher dose, as shown in Figure 12(c). The amorphous phase remained after etching, indicating that the amount of silicon etching decreased significantly in the amorphous region. Hence, the etch stop of the irradiated area was caused by the amorphization of silicon. A higher etch resistance resulted from the higher doses owing to the resulting expansion and higher density of the amorphous phase. However, by etching in HF, the amorphous phase was selectively dissolved and a concave structure was fabricated. The depth of the concave structure was determined by the longitudinal expansion of the amorphous phase when HF was used as an etchant.
Bright-field cross-sectional TEM images of a 30 keV irradiated area (a) before and (b) after etching in KOH at a low dose, and the irradiated area (c) before and (d) after etching in 20 mass% KOH at a higher dose. Doses per dot in (a) and (c) were 0.9 pC and 1.4 pC, respectively. (e) Nano-ED pattern of the irradiated area denoted by A, B, and C in (a) [59].
As shown in Figure 12, the morphology and the etch rate of the amorphous phase were different according to the irradiation conditions. The height of the structure can be controlled with this technique. Figure 13 demonstrates the relationship between the height of the structure and the ion dose [59]. The silicon surface was irradiated by Ga+ ions at various doses and then etched in KOH. The etch rate of the irradiated area decreased with increasing ion doses up to 10.0 µC/cm2. Therefore, higher structures were fabricated using higher doses. For doses over 10.0 µC/cm2, the etch rate and height were nearly constant at approximately 24 nm/min and 85 nm, respectively. For doses less than 10.0 µC/cm2, the amorphous phase induced by the ion irradiation was etched, due to the thinner and lower density amorphous phase at low dose condition. The etch resistance at low dose condition varied according to the ion doses, due to the differences in thickness and density of the amourphous phase. Therefore structures of various heights were fabricated owing to the time lag of the dissolution in KOH. A thick and highly dense amorphous phase formed when higher doses of irradiation were used, resulting in a high etch resistance against KOH. The resulting structure was somewhat also etched in KOH because the height of structure was approximately 35 nm lower than the etched depth of the non-irradiated area. This indicates that the amorphous phase formed in the interior of silicon. Therefore, the maximum etch resistance occurred in the interior of silicon, and the resulting height was somewhat less than that of the non-etched area.
AFM topography image of a FIB-irradiated area at doses of 0.6 to 9.1 µC/cm2 and an ion energy of 30 keV. (b) The same area after etching in 20 mass% KOH for 5 min. (c) Change in the height of the structure for various ion doses [59].
The height of the structure can be controlled also by the ion energy. Figure 14 shows the relationship between the ion energy and the height of a structure fabricated after etching in KOH for 5 min [61]. The height of the structure decreased with increasing ion energy at an ion dose of 25 µC/cm2, whereas the height remained constant at an ion dose of 150 µC/cm2. For the lower dose, an amorphous phase formed in the interior of the silicon and the depth of amorphous region increased with the ion energy owing to the dissolution of the non-damaged silicon above the amorphous phase. A lower structure formed at the higher ion energy owing to the increase in the projected range of the irradiated ion. However, an amorphous phase formed from the surface at the higher dose so that the resulting height of the structure was constant for all ion energies. These results indicate that the height of the structure can be controlled by adjusting the ion energy and taking advantage of the difference in depth of the amorphous phase produced by ion irradiation.
Height change of the structure as a function of the ion energy.
A protruding three-dimensional structure can be fabricated by using the methods described above [59]. Figure 15(a) shows an AFM topography image of the stepped structures fabricated using three different doses of FIB irradiation followed by wet chemical etching in KOH. The etch resistance increased with the ion dose, resulting in a higher structure under the high dose condition. Therefore, a single structure with multiple heights can be fabricated by changing the ion dose. Smooth and sloped three-dimensional dome-shaped structures can also be fabricated using this method by continuously changing the ion dose, as shown in Figure 15(b).
Application of FIB and wet chemical etching to three-dimensional fabrication. AFM topography images of a (a) stepped structure and (b) dome structure [59].
In this section, we describe a three-dimensional fabrication method based on a FIB-induced etching enhancement. In the etching enhancement, the shape of the structure was decided by the morphology of the amorphous phase because the structure was fabricated by the selective dissolution of the amorphous phase. Therefore, a three-dimensional structure was fabricated using the change in morphology of the amorphous phase according to the ion irradiation conditions.
Figures 16(a) and (c) show AFM topography images of the silicon surface (5 × 5 µm2 area) irradiated with 30 keV Ga+ ions at doses of 0.2 to 27.1 µC/cm2 and 224.0 to 2016.0 µC/cm2, respectively [61]. The irradiated area protruded at a height of 1 to 2 nm under the lower dose conditions. Under the higher dose conditions, the irradiated area was sputtered and concave structures were fabricated. A burr-like structure also formed around the edge of the irradiated area owing to the reattachment of the sputtered ions. Figures 16(b) and (d) show the AFM topography images of the same areas after etching in 46 mass% HF for 20 min. The irradiated areas were selectively etched in HF, and concave structures were fabricated. In addition, the burr-like structure shown in Figure 16(c) was entirely removed, leaving a smooth surface around the irradiated area. Thus, precise structures could be fabricated in spite of the sputtering that occurs owing to the simultaneous etching of the reattached atoms. However, for lower doses, the irradiated area was scarcely etched.
AFM topography image of a silicon surface showing the change in the irradiated area. The areas were irradiated at doses of (a) 0.2 to 27.1 µC/cm2 and (b) 224.0 to 2016.0 µC/cm2. (c) and (d) The same areas after etching in 46 mass% HF for 20 min [61].
Figure 17 shows the dependence of the depth of the structure on the dose after etching in HF for 20 min [61]. The irradiated area protruded at a dose of less than 1120 µC/cm2. At this value, the irradiated area was sputtered and a concave structure was fabricated. The irradiated area was scarcely etched by HF when the dose was less than 6.9 µC/cm2. The depth of the irradiated area rapidly increased above this value, whereas a more gradual increase was observed at doses greater than 20.4 µC/cm2. Amorphization initially occurs near the most heavily damaged region, where most of the irradiated ions have slowed and have low energies, which is shown in Figure 12. Therefore, at lower doses, an amorphous phase is formed in the interior of the silicon near the range of the irradiated ions, while the surface area recrystallizes or is not transformed to an amorphous phase. This crystalline surface layer causes the surface of the irradiated area to be scarcely etched by HF. An amorphous phase forms on the surface at the higher doses owing to the expansion, resulting in dissolution of the irradiated area in HF. A deep structure is fabricated when the dose increases because of the longitudinal expansion of the amorphous phase. Hence, the depth of the structure can be controlled by the ion dose.
Relationship between the dose and depth from the surface.
The structure depth can also be controlled by the ion energy. Figure 18 shows the relationship between the ion energy and the depth of the structure after etching in HF for 20 min [61]. The depth of the irradiated area was proportional to the ion energy for both doses. The projected range of the irradiated ions increases with the ion energy, resulting in the formation of a thick amorphous phase and therefore a deep structure. Though the maximum depth of the structure was approximately 100 nm owing to the ion energy limitations of conventional FIB instruments, deeper structures over several hundreds of nanometers deep can be fabricated by using a high-energy ion irradiation facility, which can irradiate ions at several hundreds of keV [60].
Relationship between the ion energy and depth from the surface.
Because the depth of the structure can be controlled by the ion irradiation conditions such as the dose and the ion energy, a complex three-dimensional structure can be fabricated. Figure 19(a) shows an AFM topography image of a silicon surface irradiated with four different doses [61]. The irradiated area protruded owing to the formation of an amorphous phase, but the height difference was only a few nanometers. Figure 19(b) shows an AFM topography image of the same area after etching in 46 mass% HF for 20 min. The depth increased with increasing dose values owing to the change in the thickness of the amorphous phase, and consequently, a stepped structure with four different depths was fabricated from the irradiated area.
Figure 20 shows an AFM topography image of a Fresnel lens pattern structure fabricated by gradually changing the ion dose. This is a three-dimensional structure with a smooth curved surface [61].
AFM topography image of a three-dimensional structure fabricated by using the change in the etching depth with the ion dose [61].
AFM topography image of a Fresnel lens pattern structure fabricated using FIB irradiation with various ion doses followed by wet chemical etching in 46 mass% HF for 20 min [61].
The EB is an instrument used for various purposes such as high-resolution surface observation (SEM observation), and resist exposure. In particular, the exposing technique can fabricate fine line patterns in what is known as EB lithography [62], used in a similar way to mask fabrication in photolithography. These methods permit the fabrication of nanometer- or micrometer-scale patterns. However, a more productive method is necessary to fabricate deep and wide structures or complex structures because the direct machining approach requires a time-consuming step. Generally considered contamination, it is known that the EB irradiation causes the formation of a thin hydrocarbon layer on the surface [64–67]. The carbon is introduced by the residual gas and pump into the vacuum chamber. It reacts with the EB and is then deposited on the surface [63]. Because the etching characteristics of the irradiated material change because of EB irradiation, structures can be fabricated efficiently by combining these methods with wet chemical etching, which effectively overcomes the problems of solo-irradiation methods. This method is effective because EB irradiation facilities are used worldwide, and precise patterning, with a minimum line width of several nanometers, is possible using a very simple process. In this session, the three-dimensional fabrication technique using EB-induced carbon deposition [68] is described.
Figure 21 shows SEM and AFM images of a GaAs area irradiated using the EB at a dose of 60 mC/cm2 [68]. The irradiated area appears as a dark area in the SEM image, which indicates the formation of a hydrocarbon layer. This area was raised by 1–2 nm, as shown in Figure 21(b). The hydrocarbon layer has an etch resistance against AH solution, which consists of ammonia (NH3), hydrogen peroxide (H2O2), and water (H2O) in a ratio of NH3:H2O2:H2O = 4:1:3312 by weight. By using this phenomenon, a protruding structure can be fabricated from the irradiated area.
a) SEM and (b) AFM images of the area irradiated at an EB dose of 60 mC/cm2. Reprinted with permission from [68]. Copyright 2008, IOP Publishing.
The etch resistance of the irradiated area changes owing to the irradiation conditions, and therefore, the height of the fabricated structure can be controlled via hydrocarbon layers with different etch resistances. By controlling the etch resistance, structures with different heights can be fabricated by taking advantage of the difference in the dissolution time of the hydrocarbon layers. The change in the height of the irradiated area before and after etching in AH solution for 15 s is plotted as a function of the dose in Figure 22 [68]. The height of the hydrocarbon layer ranged from 1–3 nm and increased with the dose. After etching, the irradiated area resisted etching in the AH solution, whereas the nonirradiated area was selectively etched. Consequently, a structure higher than that present before etching was fabricated on the irradiated area. The height of the structure increased with the irradiation dose. With a high dose, a thicker hydrocarbon layer formed on the irradiated area, resulting in a high etch resistance against the AH solution.
Figure 23 shows the change in the height of the structure while etching in AH solution [68]. The increase ratio of the height in the figure denotes the average value between two plots. The height of the structure increased rapidly after etching for 15 s. It remained constant for etch times over 30 s, indicating that the etch-resistant hydrocarbon layer had completely dissolved at 15 s. Additionally, after etching for 15 s, the relative increase in height at 89 mC/cm2 was greater than the relative increase at 30 mC/cm2. The values were similar for both dose conditions for etch times over 30 s. Therefore, the difference in the height of a structure according to the irradiation dose results from the difference in the etch rate in the early stages of the etching process. Because the etch resistance of the hydrocarbon layer depends on the concentration of the AH solution, the maximum height of the structure can be controlled by the AH solution concentration [68].
Change in the height of the irradiated area before and after etching in AH solution at various irradiation doses. Reprinted with permission from [68]. Copyright 2008, IOP Publishing.
Relationship between the etch time and the height of the structure. The structures were fabricated at different doses. Reprinted with permission from [68]. Copyright 2008, IOP Publishing.
From the results described above, the height of a structure can be controlled by the irradiation condition. Figure 24 shows an AFM topography image of a grating pattern structure with a uniform height, fabricated using constant irradiation conditions [68]. The GaAs surface was irradiated by an EB with a spot size of 1 µm and then etched for 30 s. As a result, structures with a constant height of 12 nm and pitch of 5 µm were fabricated. Figure 24(b) shows an AFM topography image of a three-dimensional structure fabricated by changing the EB dose. The GaAs surface was irradiated with four different doses and then etched for 30 s, resulting in a step structure. The area irradiated with the highest dose is the highest, and the area irradiated with the lowest dose is the lowest.
AFM topography images of structures fabricated using EB irradiation and wet chemical etching. (a) A grating pattern structure fabricated using a constant EB dose. (b) A step structure fabricated using the change in etch resistance of the irradiated area with the EB dose. Reprinted with permission from [68]. Copyright 2008, IOP Publishing.
We described three-dimensional fabrication techniques using nanoscale processing and wet chemical etching. Three types of processing methods were introduced. We indicated the superiority of these methods for fabricating structures with several tens to hundreds of nanometer high (deep) structures in comparison to conventional photolithographic techniques because they are simpler and more precise. Each of the three processing methods—TNL, FIB, and EB—have distinctive characteristics. Therefore, the processing method should be decided by the desired structure shape, resolution, patterning time, cost, and other factors. TNL simply forms an etching mask because the process is operated in air. The shape is decided by the machining parameters and the tip shape, which is the key technology for this method. FIB forms an etching mask via a rapid process because the dose value needed for the mask fabrication is significantly lower than that needed for a sputtering process. Deeper structures can be fabricated using the FIB-induced etching enhancement. The drawback of this method is the lateral expansion of the irradiated ions and the high-cost instrument. EB forms a high-resolution etching mask using its low-linewidth patterning ability. The maximum height of the structure was limited to several tens of nanometers and therefore can be improved by patterning and/or etching conditions. The combination of nanoscale processing and wet chemical etching is expected to become an essential tool for emerging nanotechnology and nanoscience applications related to electronic, photonic, biomedical, and nanosystem engineering.
A new type of biomedical devices was born when technologies and facilities for Micro and Nano Electro Mechanical Systems (MEMS and NEMS) fabrication have met medical and biological issues. These new kinds of biomedical devices are able to easily control physical and chemical parameters at a very small scale, down to nanomolar concentrations and nanometric sizes [1, 2, 3]. Moreover, the integration of such a device in wearable and/or mobile systems gave them popularity among commercial devices. In this technological frame, Microneedles based devices (MNDs) were born. Their height is sufficiently large to overcome the outer natural barrier of the human body, the stratum corneum of the skin, but not enough to reach the nerves, resulting in a lack of pain [4]. Usually, MN height is ranging from 10 to 1000 μm, depending on the application and how deep in the epidermis is the specific target analyte. Then, MNs based devices act as an interface between the body of the patient and a biomedical device, whose applications can range from fluid extraction for ex-situ analysis to drug and gene delivery, from in situ diagnostic tools to targeted cell therapy [1, 2, 3, 4]. Material, length, shape of the body and the tip of the MNs drastically vary depending on the application [2, 3] and the fabrication technology, according to new needs and challenges. Biosensing systems based on MNs have to overcome the stratum corneum without pain and to detect the target analytes directly in the interstitial fluid. In those cases, more than a strategy could be used: the functionalization of the surface of MNs with a specific probe, realizing a coated MND [5], the trapping of probe molecules into a swelling material [6] or the extraction of fluids and the analysis into a microfluidic system [7] are only some examples. In Figure 1A a sketch of different MNDs for sensing purposes is shown.
(A) Sketch of different MNDs for sensing purposes together with their working conditions into the human skin. Starting from the right, they are characterized by the locus of probe-analyte interaction: Swelling bulk MNs sensors (BMNDs), where probe-analyte interaction is inside the volume of MN; hollow MNs sensors (HMNDs), where a small material sampling of ISF is analyzed on or offline; coated MNs sensors (CMNDs), whose surface is the locus of the interaction between analytes and bioprobes; planar MNs sensors (PMNDs), where the probe–analyte interaction is on a specific zone of a flat MNs surface. (B) some configurations for MNs for drugs delivery: (from left) hollow MNs present a inner cavities to immediately administration of high dose and high MW drugs; soluble and hybrid MNs for fast administration with a high doses and medium MW; coated MNs for fast administration of low doses and any MW; swelling MNs for very slow administration of high doses of smaller molecules. Reproduced with permission of Ref. [8].
Moreover, microneedle-based devices (MNDs) can combine diagnostic sensing and therapeutic administration of drugs in one single tool. From this point of view, more than a painless door to the human body, a MND represents the a perfect example of theranostic instrument, since a single device could quantify the real value of a relevant biomolecule, such as glucose, and accurately deliver a drug, the insulin, if needed. MNDs are particularly interesting as simple drug administration tools, too. In fact, the transdermal route for drug administration is a very fascinating way, not only for the very low invasiveness and the easiness of self-administration, but also for the absence of first pass metabolism. However, the intercellular lipid matrix of the epidermis consists of ceramides, free fatty acids, and cholesterol, a complex mixture of neutral lipids arranged as bilayers with hydrophobic chains facing each other (lipophilic bimolecular leaflet) [9]. Transdermal delivery works only for lipophilic uncharged drugs with low MW (<500 Da), which need low dose and continuous delivery. Moreover, components, formulations and drugs must be non-irritating and non-sensitizing. MNs can be used with both lipophilic and hydrophilic formulations, both charged and uncharged drugs, both small and oversized molecules.
For all these cases, MN configurations are illustrated in Figure 1B, where the possibility to use solving or hybrid soluble/insoluble MNs are considered.
MNDs could be integrated on printed circuit boards, flexible electronics and microfluidic channels, thus allowing a continuous monitoring of the physiological parameters with very low invasiveness, together with sustained and localized administration of drugs. MNDs can be designed for very specific applications, from the detection of skin cancer to the monitoring of metabolic pathways.
Technologies, skills and facilities for Micro and Nano Electro Mechanical Systems (MEMS and NEMS) fabrication are the key elements for the development of new biomedical devices [1, 2, 3, 10]. Fabrication methods for Microneedles (MNs) strongly depend on the MNs shape, tip model, length, density of the MNs matrix, and the material of which they are made of.
Moreover, structural characteristics of the MNs matrix in turn depend on the specific application considered [11]. In fact, MNDs are exploited in fluid extraction [12] and in-situ diagnosis of diseases [13], in drug and gene delivery strategies [1, 11], in cell therapy [3] and so on.
At first, Silicon and silicon-based nanostructured materials, such as porous silicon, were largely employed in MNDs fabrication due to the well-established functionalization chemistry protocols and fabrication techniques, extenseively used in microelectronics, which simplified the integration into more complex systems [14]. However, silicon revealed to be a non-biocompatible material, due to its fragility and to the local inflammations (silicosis) it could provoke; for this reason its use has been limited in cell applications [15].
To overcome limitations on the use of silicon, polymers have been extensively proposed as alternative materials in many applications. Poly Dimethyl Siloxane (PDMS) is one of the most used materials in microfluidics to design biomedical devices, due to its well-known biological compatibility [16]. Usually, PDMS is employed as mold to fabricate MNDs by replica molding (see Figure 2). In case of PDMS molding, the fabrication involves the following steps: female PDMS mold fabrication by means of standard photolithography or laser drilling; patterned MNs in PDMS mold filling with liquid polymers in vacuum conditions; curing of the polymers by temperature and/or UV exposure; mold removal; eventually, an additional curing step [16]. Biodegradable polymers have been largely employed in MNDs for drugs delivery application [20, 21, 22, 23, 24], but the biodegradability is not required for biosensing.
Main fabrication strategies for MNs fabrication. Replica molding [16] centrifugal lithography [17] photolithography [18] drawing lithography [19].
A direct method for MNDs fabrication is the so-called drawing lithography [19]. Drawing lithography is a fabrication method, which does not need light irradiation and a mask, since it is based on the use of a thermosetting polymer directly drawn from a 2D solid surface (see Figure 2). In drawing lithography, commercial photoresist is usually spin coated or drop casted onto the substrate and cooled down. Drills are fixed in an array on a PDMS frame and used as pillars contacted with the photoresist. Conical-shaped bridges between the substrate and the pillars appear when their relative distance is increased by drawing (elongation). The bridges are cured to generate a rigid structure. Finally, the separation of the bridges produces the desired MND.
However, drawing method lacks in flexibility and the curing at high temperature of the polymers encapsulating biopharmaceutical molecules can cause their denaturation or inactivation. In fact, MNDs encapsulating drugs or bioprobes must be fabricated in a controlled environment to preserve the biological activity.
The increasing demand for simple methods that preserve the biological activity by utilizing the natural properties of polymers has conducted to the idea of centrifugal lithography [17]. In [17], centrifugal lithography was used for the fabrication of MNDs in a single centrifugation, by exploiting the self-shaping properties of hyaluronic acid (HA). Briefly, fabrication involves the following steps: HA drops encapsulating drugs molecules are casted onto the substrate; centrifugal force is applied under refrigerated conditions (4°C) to the droplets in order to shape in hourglass microstructures; finally, the mirroring shapes are separated to form MNs. Also in the case of HA, drug delivery is successfully obtained, but biosensing is unavailable due to its biodegradability.
On the other hand, hydrogel polymers are very attractive materials for MNDs and, generally, for biomedical devices, since a hydrated gel provides near physiological conditions. These gels are excellent encapsulation matrices for biological probes, such as enzymes and peptides [18, 20, 25, 26]. Moreover, the standard photolithographic processes can be employed to fabricate micrometric devices based on polymeric hydrogels [materials] (Figure 2). In [6, 18, 27, 28], authors proposed procedures of standard direct photolithography, where a mixture of Poly(ethylene glycol) diacrylate (PEGDA) and a commercial photoinitiator were used as an ordinary photoresist, without any etching step being required. In fact, PEGDA is a biocompatible polymer that solidifies at room temperature in presence of a photoinitiator after exposure to ultraviolet (UV) light for few seconds. In case of photolithographic process, the fabrication involves the following steps: the liquid photosensitive polymeric mixture is casted onto a UV-transparent substrate and exposed to ultraviolet radiation, in order to fabricate the MNDs base; a vessel is fulfilled with a second quantity of liquid mixture and the MNDs base is put on; a second exposure through a mask, whose pattern is an array of holes, is applied; finally the structure is developed by simply washing in deionized water. The PEGDA mixture can be customized to encapsulate a variety of drugs or sensing probes as biological molecules or inorganic nanoparticles [29, 30, 31].
Comparing the fabrication methods, all produced MNs have demonstrated high quality in indentation proof and a good grade of reproducibility, with some critical issues during the mold removal step in replica molding method.
Finally, we highlight that the photolithographic approach allows the fabrication of MNDs for a wide range of applications. In fact, this process allows the design of a wide range of MN types with different shape, length and tip, simply by adjusting the exposure parameters or shape photolithographic masks [18, 28]. In Figure 3, the whole range of possibilities enabled by photolithographic method are summarized: mask type 1 (simple circle) enables MNs with several heights depending on time exposure; mask type 2 (ring) enables hollow MNs with height and closure depending on time exposure; mask type 3 (mismatched concentric ring) enables in a single exposure the fabrication of hollow MNs with a lateral oblique aperture as in hypodermic syringes. Also in this case, lateral aperture is smaller as the exposure time increases.
The photolithographic methods offer a wide range of solutions for MNDs. Changing time exposure and/or photolithographic mask several configurations and arrays of MNs for both therapeutics and biosensing can be fabricated. From above: Mask type 1 (simple circle) enables MNs with several heights depending on time exposure; mask type 2 (ring) enables hollow MNs with height and closure depending on time exposure; mask type 3 (mismatched concentric ring) enables in one only exposure hollow MNs with a lateral oblique aperture, which is smaller as the exposure time increases.
MNs represent actually a flexible technological platform, which enables innovative diagnostic solutions and breakthrough therapeutic issues in biomedicine [1, 2, 3]. First, finding a painless alternative to hypodermic injections has driven researchers to the development of MNDs. In fact, belonephobia, which is the unreasonable fear of needles, affects up to 10% of the population and has implications for treatment and follow up, especially in the pediatric patients [32]. In reverse, the sensation caused by MNs has proved to be statistically indistinguishable from a smooth surface and the pain caused by a hypodermic needle has been perceived substantially more than MNs [4]. Moreover, as previously stated, the transdermal route for drug administration is a very fascinating way, not only for the very low invasiveness and the easiness of self-administration, but also for the absence of first pass metabolism. However, the intercellular lipid matrix of the epidermis consists of ceramides, free fatty acids, and cholesterol, a complex mixture of neutral lipids arranged as bilayers with hydrophobic chains facing each other (lipophilic bimolecular leaflet) [9]. Transdermal delivery works only for lipophilic uncharged drugs with low MW (<500 Da), which need low dose and continuous delivery. Moreover, components, formulations and drugs must be non-irritating and non-sensitizing. MNs can be used with both lipophilic and hydrophilic formulations, both charged and uncharged drugs, both small and oversized molecules. In fact, currently, interesting MNDs are involved in clinical trials both for some topical applications, as analgesic compounds, anti-inflammatory or anesthetic drugs, and for some traditional systemic drugs, such as anticancer drugs, vaccines, insulin or hormones [33].
Among the topical applications, MNDs can replace very invasive methods for warts therapy, such as electrocautery and cryotherapy. A MND developed by Ryu et al. for warts treatment resulted to be innovative and effective [34]. In this study, quite 40 patients with wart lesions were enrolled and referred less pain than cryotherapy, as well as more tolerability with respect to electrocautery. Other skin diseases have been treated by means of MNDs, as melasma in [35], where authors fabricated biocompatible polymeric MNs based on methacrylic acid and polyvinyl pyrrolidone (PVP) to locally administer tranexamic acid, an innovative molecule that inhibits excessive melanin production by acting on melanocytes.
Acne vulgaris is another common inflammatory skin disease, affecting both physiologically and psychologically on patients. Barrier properties of skin strongly limit the usual antibiotic drug creams used to cure acne, but the use of MNs can overcome this limits, by using a reactive oxygen species–responsive [36]. In some in-vivo studies, MNDs for anti-acne therapy demonstrated bioresponsivity and efficiency to prevent bacterial growth. Finally, among the local administration taking advantage of MNs, the treatment of cornea diseases must be quoted. In particular, using dissolving polymeric microneedles to deliver besifloxacin to the cornea, a significant improvement in besifloxacin deposition and permeation were proven after only 5 minutes of application [37].
On the other hand, also administration of systemic drugs by means of MNDs showed good results in effectiveness, safe and economic efficiency as disposal devices. A wide range of molecules has been proven to be compatible with MNDs and each category of drug showed specific advantages compared to the use of oral or hypodermic administration.
First of all, vaccine delivery is probably the most involved health issue in MN technology, due to the large number of people involved each year. Nguyen and Park recently reviewed MNDs enrolled in human studies and reported the progress of MNDs in the clinical trials [38]. Finally, the use of MNs in therapy for clinical vaccine was recognized as very important, but further tests are recommended.
When MNDs is used to deliver vaccines based on DNA, some studies show that the gene expression is improved with respect to the results of conventional hypodermic injection. Consequently, the use of MNs to administrate DNA based vaccine results in an improvement of the immune responses [38, 39]. In [39], Authors hypothesized that the improvement of the immune response by delivering DNA vaccine by means of MNs could be due to the enhancement of the protein expression of the encoded gene.
Another important issue of vaccine administration improved by MNDs is the stability of the active ingredients into dissolving or swellable MNs. Encapsulation of inactivated polio vaccine (IPV) into dissolving MNs gains a better thermal stability with respect to that of the conventional liquid formulation of IPV [40]. The greater thermostability of the MN patches can generally enable a mass distribution with less constrains on cold chain storage resulting in a great reduction of costs, since global vaccination strategies require large immunization coverage. Moreover, new MNDs have been proposed as an alternative solution to the standard needle injections, for the advantage of self-vaccination.
Further studies have been done to elucidate the interactions between polymers and vaccines, as in the case of hydrogel based MNs and dissolving MNs. In these cases, the antigen ovalbumin was used as a model protein interaction with polymers and the consequences on the immune response [40, 41].
Hollow MNs have the advantage of overcoming the skin barrier imposed by the stratum corneum and delivering bigger molecules, such as macromolecules or nanoparticle systems, in the fastest possible way. Polymeric nanoparticles encapsulating the model antigen ovalbumin have been intradermal delivered by means of hollow MNDs by Niu et al., reporting that this kind of delivery is a promising approach to improve the effectiveness of vaccine formulations [42]. Among the dissolving devices, MNs based on hyaluronic acid (HA) resulted a promising encapsulation method of high content of antigen molecules in intradermal vaccination [43].
Also anticancer drugs belong to an important field of application of MNDs: two research groups have investigated on DOX administration by means of MNs in [44] and in [45]. Nguyen et al. found in vitro studies that Polyvinyl Alcohol (PVA) MNs enhance the transdermal delivery of DOX. In an in vivo antitumor study of Hao et al., a near-infrared responsive PEGylated gold nanorod (GNR-PEG) and DOX-loaded dissolvable HA-based microneedle (GNR-PEG&DOX@HA MN) has been developed against cancer of epidermis. In the study, mice treated with GNR-PEG&DOX@HA MNs taken remarkable advantage in antitumor efficacy in only one treatment, such that all mice have been cured without recurrence.
Moreover, lipophilic drugs found a lot of benefits from the use of MNs: poorly soluble drugs were encapsulated and easily administrated by MNDs, as in the case of the widely used specific 5-HT3 receptor antagonist, namely granisetron, that prevents nausea and vomiting during emetogenic chemotherapy in cancer patients [46]. In vivo results in [46] proved the evidence of controlled release systemic delivery.
An innovative pharmaceutical solution involving a MND in the field of HIV treatment has been proposed by Yavuz et al. in [47]. Also in this case, the self-injection route of administration represents the key issue for care improvement, since it limited the risks of contamination of the personnel involved in therapy and guaranteed a painless delivery for the patients via patches of microneedles.
New drugs and innovative therapies have been put in place with the help of MNDs. In particular, polymeric MNs have been widely exploited for their porous nature, which is expressed both by soluble MNs and by simply biocompatible ones. In [48, 49], anti-obesity substances have been successfully administered. These substances modified the metabolic process by increasing the energy consumed and transforming the white fat that stores calories into brown fat that burns calories [48]. While in [49], gelatin MNDs were used to induce lipolysis and suppress adipocyte lipogenesis in fatty rats.
Particular attention has to be paid on insulin delivery, since diabetes is one of the most common diseases, not only in elder patients, but also in obesity-affected patients.
Avoiding use of enzymes, a polymeric MND has been developed for on-demand insulin delivery by Chen et al. [50]. Continuous and acute glycemic control was realized with a long-acting, safe, stable, economically efficient and on-demand insulin delivery by MND, without depending on patient compliance. Thus, this technology opens to next generation of diabetes therapies.
In the same field, the treatment of individuals with type II diabetes mellitus has been successfully obtained with metformin HCl, the most widely used drug for this disease, delivered by means of hydrogel MNs [51].
In [52], authors proposed a temperature-independent MND for glucose-responsive insulin release. The rapid and sustained regulation is enabled through a “skin layer” of Phenylboronic acid (PBA), formed on the surface of MNs. PBA is a synthetic hydrogel with reversible binding capability with glucose. Compared to other glucose-responsive MNDs based on nanoparticles or glucose oxidase, the proposed patch overcomes the safety concerns and provides a good sustainability for large-scale production. In Figure 4, a sketch of the proposed glucose-responsive insulin dispensing MND is presented together with main results in on-demand insulin release at physiological temperature.
Adapted with permission from ACS Appl. Polym. Mater. 2020, 2, 7, 2781–2790. Copyright (2020) American Chemical Society. Sketch of device and in vitro FITC-labeled insulin release at various temperatures, pH 7.4.
Finally, we cite the engage of MNDs in effective administration of small peptides, vitamin K and mRNA administered, both in vitro and in vivo studies [53, 54, 55, 56].
In Table 1, main studies on therapeutic delivery with MNDs are summarized. Another important issue is the integration of MNs in optical, microelectronic or microfluidic devices. In [6], authors present the proof-of-concept of an optical integrated MNDs based on polymeric MNs and porous silicon (PSi) for transdermal drug delivery (Figure 5). Since its surface can be chemically modified, PSi is one of the most popular porous material used in drug administration [57]. Moreover, PSi structures have a tunable refractive index that depends on their porosity [58]. The MND presented in [6] is based on PEGDA hydrogel MNs and includes a PSi free-standing membrane with a Bragg mirror optical structure, i.e. an optical structure that reflects a specific wavelength (color) in the visible spectrum. Furthermore, the Psi membrane not only acts as a drug/biomolecules reservoir, but also it can be used to optically monitor the released drug, since the reflected wavelength changes with the emptying of pores (Figure 5). In [6], the integrated-chip optical device guarantees the optimum disposable MND, which can be self-administrated and self-wasted, once the drug has been all delivered by only looking at the color variation at naked-eye.
MN type | Disease | Experiments | Refs. |
---|---|---|---|
Swelling | Acne vulgaris | In vivo (mouse) | [36] |
Swelling | Diabetes | In vitro | [50] |
Swelling | Diabetes | In vivo (mouse) | [51] |
Swelling | Immunity (vaccines) | In vitro | [40] |
Swelling | Nausea and vomiting | In vivo | [46] |
Swelling | Keloid scar | Ex vivo | [53] |
Swelling/hybrid | — | in vitro | [6] |
Hollow | Immunity (vaccines) | — | [42] |
Dissolving | Melasma | In vivo (mouse) | [35] |
Dissolving | Ocular infection | Ex vivo (cornea) | [37] |
Dissolving | Cancer | In vitro | [44] |
Dissolving | Cancer | In vivo (mouse) | [45, 54] |
Dissolving | Immunity (vaccines) | In vivo (mouse) | [41, 43] |
Dissolving | Obesity | In vivo (mouse) | [48, 49] |
Dissolving | Vitamin K deficiency | In vitro | [55] |
Coated | Warts | In vivo (human) | [34] |
Coated | Immunity (vaccines) | In vivo (mouse) | [39] |
hybrid | Diabetes | In vivo (mouse) | [52] |
Main studies on therapeutic delivery with MNDs. Adapted from [56].
The optical integrated MND presented in [6] have got a naked-eye monitor made up with a psi membrane to follow the release of a drug loaded in.
Human interstitial fluid (ISF) is on average between 9 and 13.5 L [59, 60]. Fluid moves from the lymphatic vasculature into the interstitium, among the endothelial walls of cells, then to the blood plasma, and finally returns to the lymphatic vasculature. Analytes enter into the ISF through three paths: first, by transcellular path, through the capillaries; secondly, by paracellular path, through the cell walls; finally, by vesicular path, from the cells to the ISF [61, 62]. ISF moves within a network of glycosaminoglycans, elastin, and collagen and transports electrolytes and metabolites to muscle cells, bone cells, cartilage, tissues, organs and so on [60, 63].
Dermal ISF is localized in the extracellular spaces between the vasculature, connective tissues and the cells. A lot of research efforts have been done to develop extraction methods of ISF in order to obtain an analytical composition and understand the relationship between plasma and ISF. Table 2 summarizes the main ISF constituents, measured concentrations, and typical concentration ranges for healthy people [63].
ISF constituent | Measured concentration | Typical concentration ranges |
---|---|---|
Glucose | 4–8 mM | 4.5–8 mM |
Cortisol | 24–40 nM | Morning: 1–50 nM Afternoon: 27–42 nM |
Lactate | 1.17 ± 0.23 mM | 1–2 mM |
Lipids | 1.5 ± 0.3 μM | Not reported |
Na+ | 141 mM | 135–150 mM |
K+ | 4.4 mM | 3.8–4.9 mM |
Cl− | 110 mM | 99–117 mM |
Main ISF constituents, measured concentrations and typical concentration ranges for healthy people [63].
Since its location just under human skin (the largest human organ) and its relationship with the vasculature system, analysis of ISF has received interest for the realization of new wearable devices.
On the other hand, new diagnostic methods can sensitively, rapidly and accurately detect, analyze and monitor relevant diseases of social interest, and can lead to an effective management of healthcare. Biomarkers and biosensors research receive, then, a constantly increasing thrust.
Despite the transduction method used, innovation in standard sensing technologies is continuously pursued. Although several optical techniques, such as fluorescence, surface plasmon resonance and surface enhanced Raman spectroscopy have been exploited, electrochemical methods, based either on voltammetry or impedance spectroscopy, have been demonstrated to quantify analytes in ISF with high sensitivity and easily integration into a MND [8].
Standard electrochemical sensors are realized confining bioprobes onto an electrode surface directly immersed in a solution, as the ISF. A key issue in the innovation of electrochemical devices is the design of the so-called working electrode, that can increase the performance of the whole biosensor. The development of electrochemical engineered biosensors has been recently the focus of many research groups, which provided several fabrication strategies [64].
Electrochemical sensors based on MNs can analytically monitor biomarkers, drug release, metabolites, electrolytes and other chemical species present in dermal ISF and involved in biological functions. Recently, in [65] authors gave a proteomic characterization of the dermal ISF, extracted by means of a hollow MND. In this work, 407 proteins have been found and quantified [65]. Moreover, less than 1% of these proteins have been identified only into the ISF, confirming that the ISF is strictly connected to both plasma and serum. Then, the MNDs can be minimally invasive alternative devices to blood-derived fluids sensors with potential for real-time monitoring applications. In addition, in [66] an extremely small quantity (<1 nL) of the ISF was extracted by means of a hollow MN to measure drug concentrations and the typically painful blood drawn was avoided. In [66], the inner cavity of a hollow MN was derivatized to bind vancomycin. Optical absorbance is used as off-line transducer method, after extracting ISF with an integrated optofluidic device. The optofluidic MND detected the vancomycin in a sample volume of 0.6 nL with a limit of detection (LoD) of less than 100 nM.
Before being widely adopted into clinical practice, MNDs used as biosensors have to pursuit some general issues: a low cost fabrication; continuous monitoring and/or long-lasting working time; the possibly of integration in MEMS; the protection of the bioprobe, critical in enzyme-based detection; a good electrical conductivity (EC) for electrochemical sensing [67]. Moreover, the biofouling at the tissue–device interface must be avoided to successfully realize a wearable MND sensor [68]. According to Da Silva et al., currently, wearable sensors are still not yet ready for commercial develop, but within a few years MNDs biosensors will conquer the market [69].
In the field of MNDs for diagnostics, as well as for therapy, the approach can drastically vary with shapes and materials; Figure 1A shows a sketch of different MNDs for sensing purposes together with their working conditions into the human skin. Starting from the right, Figure 6 reports: swelling bulk MNs sensors (BMNDs), whose diagnostic approach includes a volume effect in the probe-analyte interaction that will be considered separately; hollow MNs sensors (HMNDs), where a small material sampling of ISF is analyzed on or offline [70, 71, 72]; coated MNs sensors (CMNDs), whose surface is the locus of the interaction between analytes and bioprobes [73, 74, 75, 76, 77, 78, 79, 80, 81]; planar MNs sensors (PMNDs), where the probe–analyte interaction is on a specific zone of a flat MNs surface [82].
Design of the working electrode, optical images with and without metal coating and sketch of working of the MNDs. Experimental data for glucose and lactate acid dose–response. Reproduced with permission of Ref. [8]. PEGDA, polyethylene glycol diacrylate; FAD, flavin adenine dinucleotide.
The bulk volume of solid MNs (BMNDs) is often exploited in electrochemical biosensing. Usually, hydrogels and swelling polymers are employed in the fabrication of BMN. Examples are polyethylene glycol diacrylate (PEGDA), polyvinyl pyrrolidone (PVP), polyvinyl alcohol, poly(acrylic acid), poly-l-lactide, poly(lactide-coglycolide acid) and poly-N-isopropylacrylamide [83, 84]. These types of polymers can be processed by several fabrication techniques, such as replica molding, photolithography, drawing lithography and more [85]. Usually, probes and enhancers of transduction mechanisms are directly embedded in the porous polymer matrix during the fabrication. This environment protects probes without avoiding interaction between target analytes and bioprobes.
Caliò et al. trapped enzymes with vinyl-ferrocene mediator into a polymeric matrix of PEGDA in order to detect glucose and lactate exploiting the volume effect of the hydrogel matrix [27]. After being in contact with the ISF, the PEGDA matrix swells and the analytes solved into ISF enter the volume of the MNs, where a large number of probe molecules (enzymes) can be stored. The redox reaction takes place inside the volume and is transmitted to the electrode. The fabrication of the electrochemical MN biosensor only required a single further step (metal coating) in addition to the direct photolithographic process. The hybrid device traps GOx and LOX enzymes to enable the electrochemical detection of glucose and lactic acid, respectively, in physiological solution. The sensing MND showed a linear response from 0 to 4 mM for glucose, and from 0 to 1 mM for lactic acid (Figure 6) and a LoD of about 1 μM was found for both cases. Figure 6 shows design of the MN based working electrode, optical images with and without metal coating and a sketch of the working principle of the swelling MNDs. Moreover, experimental data for glucose and lactate acid dose–response are reported.
Appeared on scene as a painless alternative to syringes, MNDs have conquered the biomedicine. The flexibility of these innovative devices makes these technological platforms really attractive for even new fields of application. Almost all materials can be used in the fabrication of MNDs: noble metals (gold and silver), semiconductors (silicon), plastics (polymers and hydrogels), amorphous materials (ceramics) and artificial nanostructured materials (porous silicon). MNDs have been used for drug delivery, cosmetic industry or biosensing, where the MN microstructures have been used as electrodes for electrochemical transduction. For biosensing systems, pros and cons have been highlighted for each device type in terms of analytical performances such as LoD, detection time, sensitivity and so on. In all the application cases, considerations about the safety of MNDs is due, since MNDs are conceived for being in contact with the human body. Then, inert, biocompatible, or physiologically dissolvable materials have to be engaged for device fabrication, even if they show lower analytical or delivery performances. After the overcoming of the skin natural barrier, MNs are directly in contact with human ISF. Hollow, coated, and swelling MNDs are all used in two ways: sensing of analytes and delivery of drugs; biosensing and administration; therapy and diagnosis.
The authors declare no conflict of interest.
The Authors would like to thank all the Materias s.r.l. staff for supporting. In particular, Caterina Meglio, Aniello Cammarano, Maria Emilia Mercurio and Maria Grazia Ramaglia, those continuously help our research with their work.
Customer Satisfaction is of paramount importance at IntechOpen and we take all complaints very seriously. Our Authors, their institutions, and other purchasers, if dissatisfied with the service provided, or the product purchased, can file a written complaint to IntechOpen, 5 Princes Gate Court, London, SW7 2QJ, UK or via the following e-mail address: info@intechopen.com.
',metaTitle:"Customer Complaints",metaDescription:"Our authors, their institutions and other purchasers, if unsatisfied with the service provided or the product purchased, can file a written complaint at IN TECH d.o.o offices at Janeza Trdine 9, 51000 Rijeka, Croatia, or via the following e-mail address: info@intechopen.com.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Receipt of complaints will be acknowledged in writing and Intech Limited will respond fully to concerns within 15 business days.
\\n\\nCustomers have the right to terminate the contract without giving any reason (written notice of termination). The deadline for said termination is fourteen (14) days from the date of receipt of goods. Returns are at the expense of the Customer and must be made within the fourteen (14) days from the date of the written notice of termination. Intech Limited will process refunds to the Customer without undue delay.
\\n\\nIn the event that the Publisher ships damaged or misbound copies of products, or duplicate or incorrect copies of the products are received by the Customer, the Publisher will accept returns at the Publisher's expense, provided notice of such damaged or incorrect shipment is given to the Publisher within fourteen (14) working days from the date of receipt.
\\n\\nPublishing errors, including but not limited to typographical errors, having no significant effect on the editorial content or design characteristics of the products, cannot be considered a reason for rejecting payment or, as the case may be, modifying the agreed price.
\\n\\nAt the Publisher's request, the customer should provide evidence of the damaged or incorrect shipment. The Publisher will refund or ship the ordered products without delays.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Receipt of complaints will be acknowledged in writing and Intech Limited will respond fully to concerns within 15 business days.
\n\nCustomers have the right to terminate the contract without giving any reason (written notice of termination). The deadline for said termination is fourteen (14) days from the date of receipt of goods. Returns are at the expense of the Customer and must be made within the fourteen (14) days from the date of the written notice of termination. Intech Limited will process refunds to the Customer without undue delay.
\n\nIn the event that the Publisher ships damaged or misbound copies of products, or duplicate or incorrect copies of the products are received by the Customer, the Publisher will accept returns at the Publisher's expense, provided notice of such damaged or incorrect shipment is given to the Publisher within fourteen (14) working days from the date of receipt.
\n\nPublishing errors, including but not limited to typographical errors, having no significant effect on the editorial content or design characteristics of the products, cannot be considered a reason for rejecting payment or, as the case may be, modifying the agreed price.
\n\nAt the Publisher's request, the customer should provide evidence of the damaged or incorrect shipment. The Publisher will refund or ship the ordered products without delays.
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5766},{group:"region",caption:"Middle and South America",value:2,count:5227},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10367},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15789}],offset:12,limit:12,total:118188},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"24"},books:[{type:"book",id:"10764",title:"Antenna Systems",subtitle:null,isOpenForSubmission:!0,hash:"2fbf1c7a5d92723f08198fc9b526a8ad",slug:null,bookSignature:"Prof. Hussain Al-Rizzo and Dr. Said Abushamleh",coverURL:"https://cdn.intechopen.com/books/images_new/10764.jpg",editedByType:null,editors:[{id:"153384",title:"Prof.",name:"Hussain",surname:"Al-Rizzo",slug:"hussain-al-rizzo",fullName:"Hussain Al-Rizzo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10964",title:"Wearable Technologies",subtitle:null,isOpenForSubmission:!0,hash:"0981ee7867892cc6e0a4edd65b792ac9",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10964.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:14},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:3},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:24},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:2},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Social Sciences",value:23,count:2},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:2},popularBooks:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9043",title:"Parenting",subtitle:"Studies by an Ecocultural and Transactional Perspective",isOpenForSubmission:!1,hash:"6d21066c7438e459e4c6fb13217a5c8c",slug:"parenting-studies-by-an-ecocultural-and-transactional-perspective",bookSignature:"Loredana Benedetto and Massimo Ingrassia",coverURL:"https://cdn.intechopen.com/books/images_new/9043.jpg",editors:[{id:"193200",title:"Prof.",name:"Loredana",middleName:null,surname:"Benedetto",slug:"loredana-benedetto",fullName:"Loredana Benedetto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5229},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"856",title:"Risk Management",slug:"environmental-sciences-environmental-health-risk-management",parent:{title:"Environmental Health",slug:"environmental-sciences-environmental-health"},numberOfBooks:1,numberOfAuthorsAndEditors:26,numberOfWosCitations:56,numberOfCrossrefCitations:38,numberOfDimensionsCitations:88,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"environmental-sciences-environmental-health-risk-management",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"5184",title:"Environmental Health Risk",subtitle:"Hazardous Factors to Living Species",isOpenForSubmission:!1,hash:"aa20266ad595ce73a9396f4ab0f8112e",slug:"environmental-health-risk-hazardous-factors-to-living-species",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5184.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,mostCitedChapters:[{id:"50482",doi:"10.5772/63094",title:"Pesticides, Environmental Pollution, and Health",slug:"pesticides-environmental-pollution-and-health",totalDownloads:5401,totalCrossrefCites:25,totalDimensionsCites:54,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Arzu Özkara, Dilek Akyıl and Muhsin Konuk",authors:[{id:"5974",title:"Prof.",name:"Muhsin",middleName:null,surname:"Konuk",slug:"muhsin-konuk",fullName:"Muhsin Konuk"},{id:"179732",title:"Dr.",name:"Dilek",middleName:null,surname:"Akyıl",slug:"dilek-akyil",fullName:"Dilek Akyıl"},{id:"179733",title:"Dr.",name:"Arzu",middleName:null,surname:"Özkara",slug:"arzu-ozkara",fullName:"Arzu Özkara"}]},{id:"49818",doi:"10.5772/62049",title:"Amoxicillin in the Aquatic Environment, Its Fate and Environmental Risk",slug:"amoxicillin-in-the-aquatic-environment-its-fate-and-environmental-risk",totalDownloads:2539,totalCrossrefCites:6,totalDimensionsCites:16,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Armando Elizalde-Velázquez, Leobardo Manuel Gómez-Oliván,\nMarcela Galar-Martínez, Hariz Islas-Flores, Octavio Dublán-García and Nely SanJuan-Reyes",authors:[{id:"179818",title:"Dr.",name:"Leobardo Manuel",middleName:null,surname:"Gómez-Oliván",slug:"leobardo-manuel-gomez-olivan",fullName:"Leobardo Manuel Gómez-Oliván"}]},{id:"50234",doi:"10.5772/62455",title:"Environmental Effects of Endocrine-Disrupting Chemicals: A Special Focus on Phthalates and Bisphenol A",slug:"environmental-effects-of-endocrine-disrupting-chemicals-a-special-focus-on-phthalates-and-bisphenol-",totalDownloads:2224,totalCrossrefCites:1,totalDimensionsCites:5,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Pinar Erkekoglu and Belma Kocer-Gumusel",authors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"},{id:"185037",title:"Dr.",name:"Belma",middleName:null,surname:"Kocer-Gumusel",slug:"belma-kocer-gumusel",fullName:"Belma Kocer-Gumusel"}]}],mostDownloadedChaptersLast30Days:[{id:"50482",title:"Pesticides, Environmental Pollution, and Health",slug:"pesticides-environmental-pollution-and-health",totalDownloads:5394,totalCrossrefCites:25,totalDimensionsCites:52,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Arzu Özkara, Dilek Akyıl and Muhsin Konuk",authors:[{id:"5974",title:"Prof.",name:"Muhsin",middleName:null,surname:"Konuk",slug:"muhsin-konuk",fullName:"Muhsin Konuk"},{id:"179732",title:"Dr.",name:"Dilek",middleName:null,surname:"Akyıl",slug:"dilek-akyil",fullName:"Dilek Akyıl"},{id:"179733",title:"Dr.",name:"Arzu",middleName:null,surname:"Özkara",slug:"arzu-ozkara",fullName:"Arzu Özkara"}]},{id:"50234",title:"Environmental Effects of Endocrine-Disrupting Chemicals: A Special Focus on Phthalates and Bisphenol A",slug:"environmental-effects-of-endocrine-disrupting-chemicals-a-special-focus-on-phthalates-and-bisphenol-",totalDownloads:2217,totalCrossrefCites:1,totalDimensionsCites:5,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Pinar Erkekoglu and Belma Kocer-Gumusel",authors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"},{id:"185037",title:"Dr.",name:"Belma",middleName:null,surname:"Kocer-Gumusel",slug:"belma-kocer-gumusel",fullName:"Belma Kocer-Gumusel"}]},{id:"49818",title:"Amoxicillin in the Aquatic Environment, Its Fate and Environmental Risk",slug:"amoxicillin-in-the-aquatic-environment-its-fate-and-environmental-risk",totalDownloads:2537,totalCrossrefCites:6,totalDimensionsCites:16,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Armando Elizalde-Velázquez, Leobardo Manuel Gómez-Oliván,\nMarcela Galar-Martínez, Hariz Islas-Flores, Octavio Dublán-García and Nely SanJuan-Reyes",authors:[{id:"179818",title:"Dr.",name:"Leobardo Manuel",middleName:null,surname:"Gómez-Oliván",slug:"leobardo-manuel-gomez-olivan",fullName:"Leobardo Manuel Gómez-Oliván"}]},{id:"50298",title:"Environmental Factors in Causation of Diabetes Mellitus",slug:"environmental-factors-in-causation-of-diabetes-mellitus",totalDownloads:1599,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"P.G. Raman",authors:[{id:"179146",title:"Dr.",name:"Poondy Gopalratnam",middleName:null,surname:"Raman",slug:"poondy-gopalratnam-raman",fullName:"Poondy Gopalratnam Raman"}]},{id:"50003",title:"Immunological Risks Caused by Fibrous and Particulate Substances",slug:"immunological-risks-caused-by-fibrous-and-particulate-substances",totalDownloads:781,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Shoko\nYamamoto, Tamayo Hatayama, Kei Yoshitome, Hiroaki Hayashi,\nMegumi Maeda and Takemi Otsuki",authors:[{id:"34101",title:"Prof.",name:"Takemi",middleName:null,surname:"Otsuki",slug:"takemi-otsuki",fullName:"Takemi Otsuki"},{id:"48631",title:"Dr.",name:"Yasumitsu",middleName:null,surname:"Nishimura",slug:"yasumitsu-nishimura",fullName:"Yasumitsu Nishimura"}]},{id:"50193",title:"Risks of Environmental Genotoxicants",slug:"risks-of-environmental-genotoxicants",totalDownloads:1174,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Sabry M. Attia and Gamaleldin I. Harisa",authors:[{id:"178995",title:"Prof.",name:"Sabry",middleName:null,surname:"Attia",slug:"sabry-attia",fullName:"Sabry Attia"},{id:"180300",title:"Prof.",name:"Gamaleldin",middleName:null,surname:"Harisa",slug:"gamaleldin-harisa",fullName:"Gamaleldin Harisa"},{id:"190926",title:"Prof.",name:"M. Abd Allah",middleName:null,surname:"Gamil",slug:"m.-abd-allah-gamil",fullName:"M. Abd Allah Gamil"}]},{id:"50264",title:"Occupational Exposure to Coal, Genotoxicity, and Cancer Risk",slug:"occupational-exposure-to-coal-genotoxicity-and-cancer-risk",totalDownloads:1449,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Grethel León-Mejía , Milton Quintana Sosa , Paula Rohr , Katia\nKvitko, João Antonio Pêgas Henriques and Juliana da Silva",authors:[{id:"170192",title:"Dr.",name:"Katia",middleName:null,surname:"Kvitko",slug:"katia-kvitko",fullName:"Katia Kvitko"},{id:"170193",title:"Dr.",name:"Juliana",middleName:null,surname:"Da Silva",slug:"juliana-da-silva",fullName:"Juliana Da Silva"},{id:"180743",title:"MSc.",name:"Grethel",middleName:null,surname:"Leon-Mejia",slug:"grethel-leon-mejia",fullName:"Grethel Leon-Mejia"},{id:"180880",title:"Dr.",name:"Milton",middleName:null,surname:"Quintana",slug:"milton-quintana",fullName:"Milton Quintana"},{id:"181198",title:"Dr.",name:"Paula",middleName:null,surname:"Rohr",slug:"paula-rohr",fullName:"Paula Rohr"},{id:"181199",title:"Dr.",name:"Jose Antonio",middleName:null,surname:"Pegas Henriques",slug:"jose-antonio-pegas-henriques",fullName:"Jose Antonio Pegas Henriques"}]},{id:"50341",title:"Soil Contamination Health Risks in Czech Proposal of Soil Protection Legislation",slug:"soil-contamination-health-risks-in-czech-proposal-of-soil-protection-legislation",totalDownloads:1039,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"Radim Vácha, Milan Sáňka, Jan Skála, Jarmila Čechmánková and\nViera Horváthová",authors:[{id:"85483",title:"Associate Prof.",name:"Radim",middleName:null,surname:"Vacha",slug:"radim-vacha",fullName:"Radim Vacha"}]},{id:"50454",title:"Modelling in Metal Risk Assessment",slug:"modelling-in-metal-risk-assessment",totalDownloads:1568,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"T.T. Yen Le",authors:[{id:"178989",title:"Dr.",name:"T.T. Yen",middleName:null,surname:"Le",slug:"t.t.-yen-le",fullName:"T.T. Yen Le"}]},{id:"50769",title:"Assessment of DNA Damage by Comet Assay in Buccal Epithelial Cells: Problems, Achievement, Perspectives",slug:"assessment-of-dna-damage-by-comet-assay-in-buccal-epithelial-cells-problems-achievement-perspectives",totalDownloads:1462,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"environmental-health-risk-hazardous-factors-to-living-species",title:"Environmental Health Risk",fullTitle:"Environmental Health Risk - Hazardous Factors to Living Species"},signatures:"J. Sánchez-Alarcón, M. Milić, S. Gómez-Arroyo, J. M. R. Montiel-González and R. Valencia-Quintana",authors:[{id:"15052",title:"Dr.",name:"Sandra",middleName:null,surname:"Gomez-Arroyo",slug:"sandra-gomez-arroyo",fullName:"Sandra Gomez-Arroyo"},{id:"40591",title:"Dr.",name:"Mirta",middleName:null,surname:"Milić",slug:"mirta-milic",fullName:"Mirta Milić"},{id:"179537",title:"Dr.",name:"Rafael",middleName:null,surname:"Valencia-Quintana",slug:"rafael-valencia-quintana",fullName:"Rafael Valencia-Quintana"},{id:"180673",title:"MSc.",name:"Juana",middleName:null,surname:"Sánchez-Alarcón",slug:"juana-sanchez-alarcon",fullName:"Juana Sánchez-Alarcón"},{id:"185133",title:"MSc.",name:"J Mariano R",middleName:null,surname:"Montiel-González",slug:"j-mariano-r-montiel-gonzalez",fullName:"J Mariano R Montiel-González"}]}],onlineFirstChaptersFilter:{topicSlug:"environmental-sciences-environmental-health-risk-management",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/205500/antonio-laguna-camacho",hash:"",query:{},params:{id:"205500",slug:"antonio-laguna-camacho"},fullPath:"/profiles/205500/antonio-laguna-camacho",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()