Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\n
Thank you all for being part of the journey. 5,000 times thank you!
\\n\\n
Now with 5,000 titles available Open Access, which one will you read next?
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n
"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\n\n
Thank you all for being part of the journey. 5,000 times thank you!
\n\n
Now with 5,000 titles available Open Access, which one will you read next?
\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:"4791",leadTitle:null,fullTitle:"Power Quality Issues in Distributed Generation",title:"Power Quality Issues in Distributed Generation",subtitle:null,reviewType:"peer-reviewed",abstract:"This book deals with several selected aspects of electric power quality issues typically faced during grid integration processes of contemporary renewable energy sources. In subsequent chapters of this book the reader will be familiarized with the issues related to voltage and current harmonics and inter-harmonics generation and elimination, harmonic emission of switch-mode rectifiers, reactive power flow control in power system with non-linear loads, modeling and simulation of power quality issues in power grid, advanced algorithms used for estimating harmonic components, and new methods of measurement and analysis of real time accessible power quality related data.",isbn:null,printIsbn:"978-953-51-2187-9",pdfIsbn:"978-953-51-6392-3",doi:"10.5772/59895",price:119,priceEur:129,priceUsd:155,slug:"power-quality-issues-in-distributed-generation",numberOfPages:156,isOpenForSubmission:!1,isInWos:1,hash:"e6a5af4c285e95291db0e96e4850883e",bookSignature:"Jaroslaw Luszcz",publishedDate:"October 21st 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4791.jpg",numberOfDownloads:17455,numberOfWosCitations:9,numberOfCrossrefCitations:8,numberOfDimensionsCitations:18,hasAltmetrics:1,numberOfTotalCitations:35,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 20th 2014",dateEndSecondStepPublish:"December 11th 2014",dateEndThirdStepPublish:"March 23rd 2015",dateEndFourthStepPublish:"April 8th 2015",dateEndFifthStepPublish:"May 8th 2015",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"24994",title:"Dr.",name:"Jaroslaw",middleName:null,surname:"Luszcz",slug:"jaroslaw-luszcz",fullName:"Jaroslaw Luszcz",profilePictureURL:"https://mts.intechopen.com/storage/users/24994/images/4357_n.jpg",biography:"Jaroslaw Luszcz received his M.Sc. and Ph.D. degrees from Gdansk University of Technology in Poland. Currently, he is at the Electrical and Control Engineering Faculty, Gdansk University of Technology. During fifteen years of professional experience in the area of power quality and electromagnetic compatibility, he has been involved in and led a number of grant-funded fundamental research projects and actively cooperated with power electronics industry as an EMC consultant for R&D projects. Mr. Luszcz has published over 50 scientific papers at international conferences and in journals, as well as three book chapters. His current research activities focus on EMC and power quality issues related to the integration of high power static converters with the power grid. Mr. Luszcz is a member of the IEEE EMC Society and Technical Committee 7 - Low Frequency EMC.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],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:"49069",title:"Distributed Generation and Its Impact on Power Quality in Low-Voltage Distribution Networks",doi:"10.5772/61172",slug:"distributed-generation-and-its-impact-on-power-quality-in-low-voltage-distribution-networks",totalDownloads:1908,totalCrossrefCites:2,totalDimensionsCites:5,signatures:"Tomasz Sikorski and Jacek Rezmer",downloadPdfUrl:"/chapter/pdf-download/49069",previewPdfUrl:"/chapter/pdf-preview/49069",authors:[{id:"175191",title:"D.Sc.",name:"Tomasz",surname:"Sikorski",slug:"tomasz-sikorski",fullName:"Tomasz Sikorski"},{id:"175323",title:"Dr.",name:"Jacek",surname:"Rezmer",slug:"jacek-rezmer",fullName:"Jacek Rezmer"}],corrections:null},{id:"49111",title:"Applications of Switch-Mode Rectifiers on Micro-grid Incorporating with EV and BESS",doi:"10.5772/61248",slug:"applications-of-switch-mode-rectifiers-on-micro-grid-incorporating-with-ev-and-bess",totalDownloads:1613,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"K. W. Hu and C. M. Liaw",downloadPdfUrl:"/chapter/pdf-download/49111",previewPdfUrl:"/chapter/pdf-preview/49111",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"}],corrections:null},{id:"48982",title:"A Comprehensive Modeling and Simulation of Power Quality Disturbances Using MATLAB/SIMULINK",doi:"10.5772/61209",slug:"a-comprehensive-modeling-and-simulation-of-power-quality-disturbances-using-matlab-simulink",totalDownloads:11595,totalCrossrefCites:4,totalDimensionsCites:12,signatures:"Rodney H.G. Tan and Vigna K. Ramachandaramurthy",downloadPdfUrl:"/chapter/pdf-download/48982",previewPdfUrl:"/chapter/pdf-preview/48982",authors:[{id:"152137",title:"Dr.",name:"Vigna",surname:"Ramachandaramurthy",slug:"vigna-ramachandaramurthy",fullName:"Vigna Ramachandaramurthy"},{id:"175327",title:"Dr.",name:"Rodney",surname:"Tan",slug:"rodney-tan",fullName:"Rodney Tan"}],corrections:null},{id:"49222",title:"An Application of Simple and Compact Genetic Algorithms for Estimating Harmonic Components",doi:"10.5772/61203",slug:"an-application-of-simple-and-compact-genetic-algorithms-for-estimating-harmonic-components",totalDownloads:1165,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Andre L. S. Pessoa, Pedro H. C. Ulisses, Hermes M. G. C. Branco and\nRicardo de Andrade Lira Rabêlo",downloadPdfUrl:"/chapter/pdf-download/49222",previewPdfUrl:"/chapter/pdf-preview/49222",authors:[{id:"24989",title:"Prof.",name:"Ricardo",surname:"de Andrade Lira Rabêlo",slug:"ricardo-de-andrade-lira-rabelo",fullName:"Ricardo de Andrade Lira Rabêlo"}],corrections:null},{id:"49008",title:"A Distributed Web-Based System for Temporal and Spatial Power Quality Analysis",doi:"10.5772/61145",slug:"a-distributed-web-based-system-for-temporal-and-spatial-power-quality-analysis",totalDownloads:1177,totalCrossrefCites:2,totalDimensionsCites:1,signatures:"Stefano Di Pasquale, Sabino Giarnetti, Fabio Leccese, Daniele\nTrinca, Marco Cagnetti and Maurizio Caciotta",downloadPdfUrl:"/chapter/pdf-download/49008",previewPdfUrl:"/chapter/pdf-preview/49008",authors:[{id:"175331",title:"Prof.",name:"Fabio",surname:"Leccese",slug:"fabio-leccese",fullName:"Fabio Leccese"}],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:"68579",slug:"corrigendum-to-industrial-heat-exchanger-operation-and-maintenance-to-minimize-fouling-and-corrosion",title:"Corrigendum to: Industrial Heat Exchanger: Operation and Maintenance to Minimize Fouling and Corrosion",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/68579.pdf",downloadPdfUrl:"/chapter/pdf-download/68579",previewPdfUrl:"/chapter/pdf-preview/68579",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/68579",risUrl:"/chapter/ris/68579",chapter:{id:"52929",slug:"industrial-heat-exchanger-operation-and-maintenance-to-minimize-fouling-and-corrosion",signatures:"Teng Kah Hou, Salim Newaz Kazi, Abu Bakar Mahat, Chew Bee Teng,\nAhmed Al-Shamma’a and Andy Shaw",dateSubmitted:"March 23rd 2016",dateReviewed:"October 10th 2016",datePrePublished:null,datePublished:"April 26th 2017",book:{id:"6080",title:"Heat Exchangers",subtitle:"Advanced Features and Applications",fullTitle:"Heat Exchangers - Advanced Features and Applications",slug:"heat-exchangers-advanced-features-and-applications",publishedDate:"April 26th 2017",bookSignature:"S M Sohel Murshed and Manuel Matos Lopes",coverURL:"https://cdn.intechopen.com/books/images_new/6080.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"24904",title:"Prof.",name:"S. M. Sohel",middleName:null,surname:"Murshed",slug:"s.-m.-sohel-murshed",fullName:"S. M. Sohel Murshed"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"93483",title:"Dr.",name:"Salim Newaz",middleName:null,surname:"Kazi",fullName:"Salim Newaz Kazi",slug:"salim-newaz-kazi",email:"salimnewaz@um.edu.my",position:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},{id:"187135",title:"Ph.D.",name:"Kah Hou",middleName:null,surname:"Teng",fullName:"Kah Hou Teng",slug:"kah-hou-teng",email:"alex_teng1989@hotmail.com",position:null,institution:{name:"Liverpool John Moores University",institutionURL:null,country:{name:"United Kingdom"}}},{id:"194347",title:"Prof.",name:"Abu Bakar",middleName:null,surname:"Mahat",fullName:"Abu Bakar Mahat",slug:"abu-bakar-mahat",email:"ir_abakar@um.edu.my",position:null,institution:null},{id:"194348",title:"Dr.",name:"Bee Teng",middleName:null,surname:"Chew",fullName:"Bee Teng Chew",slug:"bee-teng-chew",email:"chewbeeteng@um.edu.my",position:null,institution:null},{id:"194349",title:"Prof.",name:"Ahmed",middleName:null,surname:"Al-Shamma'A",fullName:"Ahmed Al-Shamma'A",slug:"ahmed-al-shamma'a",email:"A.Al-Shamma'a@ljmu.ac.uk",position:null,institution:null},{id:"194350",title:"Prof.",name:"Andy",middleName:null,surname:"Shaw",fullName:"Andy Shaw",slug:"andy-shaw",email:"A.Shaw@ljmu.ac.uk",position:null,institution:null}]}},chapter:{id:"52929",slug:"industrial-heat-exchanger-operation-and-maintenance-to-minimize-fouling-and-corrosion",signatures:"Teng Kah Hou, Salim Newaz Kazi, Abu Bakar Mahat, Chew Bee Teng,\nAhmed Al-Shamma’a and Andy Shaw",dateSubmitted:"March 23rd 2016",dateReviewed:"October 10th 2016",datePrePublished:null,datePublished:"April 26th 2017",book:{id:"6080",title:"Heat Exchangers",subtitle:"Advanced Features and Applications",fullTitle:"Heat Exchangers - Advanced Features and Applications",slug:"heat-exchangers-advanced-features-and-applications",publishedDate:"April 26th 2017",bookSignature:"S M Sohel Murshed and Manuel Matos Lopes",coverURL:"https://cdn.intechopen.com/books/images_new/6080.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"24904",title:"Prof.",name:"S. M. Sohel",middleName:null,surname:"Murshed",slug:"s.-m.-sohel-murshed",fullName:"S. M. Sohel Murshed"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"93483",title:"Dr.",name:"Salim Newaz",middleName:null,surname:"Kazi",fullName:"Salim Newaz Kazi",slug:"salim-newaz-kazi",email:"salimnewaz@um.edu.my",position:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},{id:"187135",title:"Ph.D.",name:"Kah Hou",middleName:null,surname:"Teng",fullName:"Kah Hou Teng",slug:"kah-hou-teng",email:"alex_teng1989@hotmail.com",position:null,institution:{name:"Liverpool John Moores University",institutionURL:null,country:{name:"United Kingdom"}}},{id:"194347",title:"Prof.",name:"Abu Bakar",middleName:null,surname:"Mahat",fullName:"Abu Bakar Mahat",slug:"abu-bakar-mahat",email:"ir_abakar@um.edu.my",position:null,institution:null},{id:"194348",title:"Dr.",name:"Bee Teng",middleName:null,surname:"Chew",fullName:"Bee Teng Chew",slug:"bee-teng-chew",email:"chewbeeteng@um.edu.my",position:null,institution:null},{id:"194349",title:"Prof.",name:"Ahmed",middleName:null,surname:"Al-Shamma'A",fullName:"Ahmed Al-Shamma'A",slug:"ahmed-al-shamma'a",email:"A.Al-Shamma'a@ljmu.ac.uk",position:null,institution:null},{id:"194350",title:"Prof.",name:"Andy",middleName:null,surname:"Shaw",fullName:"Andy Shaw",slug:"andy-shaw",email:"A.Shaw@ljmu.ac.uk",position:null,institution:null}]},book:{id:"6080",title:"Heat Exchangers",subtitle:"Advanced Features and Applications",fullTitle:"Heat Exchangers - Advanced Features and Applications",slug:"heat-exchangers-advanced-features-and-applications",publishedDate:"April 26th 2017",bookSignature:"S M Sohel Murshed and Manuel Matos Lopes",coverURL:"https://cdn.intechopen.com/books/images_new/6080.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"24904",title:"Prof.",name:"S. M. Sohel",middleName:null,surname:"Murshed",slug:"s.-m.-sohel-murshed",fullName:"S. M. Sohel Murshed"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"7642",leadTitle:null,title:"Evolutionary Computation and Recent Trends",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tThe aim of this book give a compact material on Evolutionary Computation. As it is known evolutionary computation has been used in most of the studies and will be used in future studies. So this study is aimed to satisfy the needs for a comprehensive source for Evolutionary Computation. Concepts of Evolutionary Computation, strategies for the best performing algorithm improvement, performance tests and applications on Evolutionary Computation are welcome.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:null,priceUsd:null,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"e58f531092fdf274d74855a3c295cd54",bookSignature:"Dr. Pakize Erdogmus",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/7642.jpg",keywords:"Evolutionary Computation, Evolution, Survival, Population Based Algorithms, Genetic Algorithm, Evolutionary Computation Testing, Benchmark Problems, CEC, Global Optimization, Nature-Inspired Algorithms, Evolutionary Process,Exploration, Exploitation, Convergence, Clustering, Segmentation, Regression",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 18th 2019",dateEndSecondStepPublish:"May 9th 2019",dateEndThirdStepPublish:"July 8th 2019",dateEndFourthStepPublish:"September 26th 2019",dateEndFifthStepPublish:"November 25th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"80893",title:"Dr.",name:"Pakize",middleName:null,surname:"Erdogmus",slug:"pakize-erdogmus",fullName:"Pakize Erdogmus",profilePictureURL:"https://mts.intechopen.com/storage/users/80893/images/system/80893.jpg",biography:"Pakize Erdoğmuş was born in Erzurum, Turkey, in 1972. She received her BSc degree in Electronics and Communications Engineering from Yildiz Technical University, Kocaeli Engineering Faculty, in 1993. \r\n\r\nShe received her MSc degree in Computer Science and her Ph.D. degree in Numerical Methods from Ataturk University. Dr. Erdoğmuş studied continuous optimization problems, linear programming, and revised simplex method, for her master of thesis and course scheduling 'Discrete Optimization Problem” for her Ph.D. \r\n\r\nFrom 2003 to 2010, she was an Assistant Professor at Duzce University, Faculty of Technical Education. Since 2010, she has been working in the Department of Computer Engineering of Duzce University, Faculty of Engineering. She is currently working at Duzce University, Engineering Faculty, Department of Computer Engineering as an Associate professor. \r\n\r\nHer research interests are nature-inspired optimization algorithms, signal and image processing.",institutionString:"Duzce University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Duzce University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"9",title:"Computer and Information Science",slug:"computer-and-information-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"297737",firstName:"Mateo",lastName:"Pulko",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/297737/images/8492_n.png",email:"mateo.p@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6363",title:"Particle Swarm Optimization with Applications",subtitle:null,isOpenForSubmission:!1,hash:"bd3e64f30fb874076a8a9af1f52c3caa",slug:"particle-swarm-optimization-with-applications",bookSignature:"Pakize Erdoğmuş",coverURL:"https://cdn.intechopen.com/books/images_new/6363.jpg",editedByType:"Edited by",editors:[{id:"80893",title:"Dr.",name:"Pakize",surname:"Erdogmus",slug:"pakize-erdogmus",fullName:"Pakize Erdogmus"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}}]},chapter:{item:{type:"chapter",id:"60330",title:"Preclinical Aspects on Magnetic Iron Oxide Nanoparticles and Their Interventions as Anticancer Agents: Enucleation, Apoptosis and Other Mechanism",doi:"10.5772/intechopen.74176",slug:"preclinical-aspects-on-magnetic-iron-oxide-nanoparticles-and-their-interventions-as-anticancer-agent",body:'
1. Introduction
Due to the wide potential of applications in various fields, such as biotechnology, biomedicine, magnetic fluids, catalysis, magnetic data recording and storage media, magnetic resonance imaging, magnetic fluid hyperthermia, magnetic drug delivery, cell separation, magnetic paper and more recently in environmental protection, magnetic iron oxide nanoparticles (M-IONPs) are the main components of the modern technology [1–15]. In nature, many forms of iron oxides are found, but the most technologically used are the magnetite (Fe3O4), maghemite (γ-Fe2O3) and hematite (α-Fe2O3) (Figure 1).
Figure 1.
Crystal structure of: A—hematite, B—maghemite and C—magnetite (the blue sphere is Fe2+/Fe3+ and the red sphere is O2−). The structures were adapted after the structures found in the Crystallography Open Database (http://www.crystallography.net).
Magnetite (Fe3O4), a natural mineral known as the black iron oxide, is relatively stable at room temperature, very quickly transforms in maghemite and shows the strongest magnetism compared to other transition metal oxides [16]. Fe3O4 has an inverse spinel structure with all the Fe2+ ions and half of the Fe3+ ions distributed in the octahedral sites and the other half of the Fe3+ ions distributed in the tetrahedral sites being surrounded by four oxygen atoms [17].
Spin magnetic moments of Fe3+ ions distributed in octahedral positions are parallely aligned, as well as those of Fe3+ ions distributed in tetrahedral positions but in the opposite direction, leading to an antiparallel coupling. Therefore, the spin moments of all Fe3+ ions mutually cancel out and do not contribute to the net magnetization of magnetite (Figure 2). All Fe2+ ions have magnetic moments aligned in the same direction so that their total magnetic moment is responsible for the net magnetization of magnetite. Therefore, the saturation magnetization of magnetite corresponds to the product between the spin magnetic moment of each Fe2+ ion and the number of Fe2+ ions, which corresponds to the mutual alignment of all Fe2+ ions in magnetite.
Figure 2.
Spin magnetic moment distribution of Fe2+ and Fe3+ ions in the elemental cell of magnetite.
Magnetite is oxidized in the presence of air to maghemite, which is also ferrimagnetic, but has a slightly lower magnetic response. This process is called maghemitization and occurs at the surface of the crystals. Crystal centers are also oxidized, and the process is being carried out by diffusion of Fe2+ ions from inside to the surface of the crystals, where they are converted to Fe3+. The rate of the oxidation process is determined by the diffusion rate of Fe2+ ions and the distance to the surface. Therefore, the particles remain unaffected by the phenomenon of maghemitization, while the small ones are susceptible to oxidation even at room temperature.
As magnetite, maghemite (γ-Fe2O3) has a spinel structure with the oxygen ions disposed in a closely packed cubic lattice and the iron ions located at interstices. In γ-Fe2O3 not all the sites are occupied, Fe3+ ions are regularly distributed in only two-thirds of the sites and the rest of the sites remain vacant. After two sites filled with Fe3+ ions follows one vacant site [18, 19]. Maghemite is a metastable oxide, product of magnetite oxidation or a product resulting from the heating of other iron oxides.
At temperatures over 300°C, magnetite is oxidized to hematite (α-Fe2O3)—an anti-ferromagnetic iron oxide. Hematite (α-Fe2O3) has a corundum crystal structure with Fe3+ ions distributed in octahedral sites and oxygen ions in hexagonal close-packed arrangement. α-Fe2O3, the final product of the transformation of other iron oxides, is a red powder when it is finely divided, very stable at room temperature and very widespread in rocks and soils (Table 1) [20, 21].
Property
Oxide
Magnetite
Maghemite
Hematite
Molecular formula
Fe3O4
γ-Fe2O3
α-Fe2O3
Color
Black
Reddish-brown
Red
Density (g/cm3)
5.18
4.87
5.26
Melting temperature (°C)
1583–1597
—
1350
Hardness
5.5
5
6.5
Type of magnetism
Ferrimagnetic
Ferrimagnetic
Weakly ferromagnetic/anti-ferromagnetic
Curie temperature (K)
858
820–986
956
Saturation magnetization (Ms) at 300 K [A·m2/kg]
92–100
60–80
0.3
Standard Gibbs free energy of formation (ΔGf0) [kJ/mol]
Physical and magnetic properties of iron oxides [22].
2. Properties of magnetic nanoparticles
2.1. Magnetic behavior
Magnetic iron oxide nanoparticles (M-IONPs), magnetite (Fe3O4) and maghemite (γ-Fe2O3) are materials with iron-magnetic properties under their Curie temperatures (858 K and 986 K) (Table 1). The ferro- and ferrimagnetic compounds in their raw state present a multidimensional magnetic structure, without a permanent magnetic moment. The magnetic properties of a material depend on following parameters: (i) temperature, (ii) pressure and (iii) applied magnetic field. The properties of iron oxide nanoparticles by their usual sizes are not similar to the properties of larger scale compounds, which explain their use and interest in nanomedicine [23]. In order to define the behavior of the magnetic field, the key lays in the size and distribution of nanoparticles morphology [24]. A spherical, small nanoparticle made of soft materials with a diameter below the domain size shows an expendable magnetic anisotropy, so that their magnetic moment is free to rotate relatively to the particle and is thus superparamagnetic, i.e., paramagnetic under the Curie temperature [25]. The direction of the magnetic moment of the nanoparticles is determined by thermal fluctuation and the magnetic anisotropy, which tend to fixate on the crystalline structure or particle morphology [26].
The interaction between an external magnetic field and the magnetic field of a nanoparticle determines: (i) the orientation of the magnetic moment of the particle as to become parallel with the magnetic field applied to minimize energy and bipolar interaction and (ii) the transition of the particle in the direction of the gradient, as in magnetophoresis [26]. Many applications of the magnetic nanoparticles are based on their ability to be manipulated using magnetic fields. This capability depends on the effectiveness of the magnetophoretic force, determined by the time of the particle and the magnetic field gradient, to fasten or to move the particle [25]. The magnetophoretic force exercised over superparamagnetic nanoparticles with a single core is less effective due to their small diameter and magnetic moment, but in the case of multicore particles, the magnetic momentum induced in the field is strong enough to allow magnetic targeting to moderate values of the magnetic field intensity and field gradient. Therefore, in order to assess the applicability of magnetic particles or magnetic fixing, the magnetic momentum of the particles is more relevant than mass magnetization [25, 27].
2.2. Size
The size and the size distribution of superparamagnetic iron oxide nanoparticles are important parameters for their biological application. Also, their magnetic properties are in close touch with their size. It has been demonstrated that the magnetic dipole-dipole interactions are significantly reduced in superparamagnetic iron oxide nanoparticles due to their scale of r6, r being the radius of the particle [28]. The advantages of using magnetic nanoparticles with sizes smaller than 100 nm are due to their surface efficiency to easily attach ligands and small settling velocities which give a high stability in suspension and improve tissue diffusion. Particles should be small enough to bypass the endothelial reticule system. They are supposed to remain in circulation after injection and be able to pass through the capital systems, organs and tissues, avoiding the embolus. Particle size is also important for getting an effect of improved permeability and retention. For example, particles larger than 10 nm may not penetrate the endothelium in physiological conditions, but can enter in pathological conditions, such as inflammations or tumors [28].
When magnetic nanoparticles loaded with medicinal substances are injected into the systemic circulation, size, morphology and surface charge are the three important parameters for their behavior in the bloodstream. Kupffer cells in the liver are very sensitive to both microorganisms and nanoparticles. Plasma proteins can easily adsorb onto their surface nanoparticles, depending on their size, surface charging and their morphology. Particles with sizes larger than 200 nm or below 10 nm are not suitable due to their absorption by the endoplasmic reticulum system [28].
2.3. Charge
Loading surface and biodistribution of superparamagnetic iron oxide nanoparticles play an important role in the colloidal stability. Surface charging can be described qualitatively by the nature and behavior of surface groups in the solution at a given pH and in the presence of an electrolyte. In terms of quantity, it can be measured as an electric potential in the double layer of the interfacial surface of the nanoparticles found in a suspension state. A high value of zeta potential is an indication of stability in dispersion of superparamagnetic iron oxide nanoparticles due to electrostatic interaction. Composition and structure of nanoparticles are very important for their interaction with biological fluids. In a known environment, superparamagnetic nanoparticle characteristics, such as the chemical composition, both core and neural crest cells, its size and size distribution, shape and angles of curvature, its crystalline structure, smoothness or surface roughness and hydrophobic or hydrophilic levels, are important for their in vivo applications. These features can determine their stationary time in the circulatory system [28].
Osaka and his colleagues [29] have reported a correlation between surface charge of magnetite nanoparticles and their cellular absorption efficiency on different cell lines. For example, a superparamagnetic particle with positive charge showed a greater internalization in human breast cancer cells in comparison with those charged negatively, while there was no difference in the degree of internalization in endothelial cells of human umbilical bladder. Thus, the superparamagnetic nanoparticles absorption depends not only on their surface properties but also on cell type.
2.4. Surface functionality and colloidal stability
Both the surface chemistry of magnetite particles and its properties are particularly important in various applications. Iron atoms at the surface of the magnetite particle that are not bound to oxygen atoms act as Lewis acids and coordinate the molecules that can give a pair of electrons. In aqueous systems, these atoms coordinate water molecules that rapidly dissociate resulting magnetite with functionalized surface with Fe-OH hydroxyl groups. So, the chemistry of the surface of magnetite particles is strongly dependent on the pH value; at low pH values, the surface of the magnetite particles is protonated (positively charged), and at high pH values, it is negatively charged (Figure 3). The preformed hydroxyl groups on the surface of magnetite have amphoteric character; therefore, they can react either as acids or bases [30].
Figure 3.
The behavior of Fe3O4 nanoparticles depending on pH.
Another problem that arises after obtaining the magnetic iron oxide nanoparticles (M-IONPs) is their agglomeration that is installed due to the van der Waals forces and the magnetic forces. Nanoparticles without coatings (naked nanoparticles) are not stable in aqueous environments, easily aggregating and precipitating. After application in vivo, nanoparticles often form aggregates in the bloodstream and are retained by the macrophages. Therefore, they must be covered with a variety of fragments which have the property to eliminate or minimize their aggregation in physiological conditions [31]. The magnetic nanoparticles are coated with an impervious wrapper so that oxygen does not reach at the surface of the magnetic nanoparticles in order to ensure an effective stabilization of iron oxide nanoparticles. Some stabilizers, such as a surfactant or a polymer, usually are added during preparation to prevent the aggregation of nanosized particles. Most of these polymers stick to the nanoparticles surface in a specific substrate manner. Nanoparticle surfaces can be composed of several organic and inorganic materials, including polymer. Also, polymer coating materials can be classified in turn into synthetic and natural. Polymers such as poly-ethylene-co-vinyl acetate, poly-vinylpyrrolidone, poly-acid-lactic-co-glycolic, polyethylene glycol, etc. are typical examples of synthetic polymeric systems. Natural polymer coatings include gelatin, dextran, chitosan, etc. The molecules used for stabilization of magnetic nanoparticles must be biocompatible and biodegradable. The most common surfactant molecules are oleic acid, lauric acid, acids, sulfonic acids, alkanes and alkane phosphonates. The surfactants are amphiphilic compounds and they manifest their role at the interface between nanoparticles and solvent. However, magnetic nanoparticles covered with organic compounds, in suspension cannot be used for biological purposes, especially in the delivery of medicines. Changing the surface of nanoparticles post-synthesis is known as core-shell nanoparticles, also used widely. The most commonly used materials are polymers, silica or metals (e.g. gold, cadmium, selenium, silver). Coating materials protect the core against oxidation and therefore keep the magnetic property of nanoparticles. It is known that the iron oxide nanoparticles are non-toxic, but some coating materials may be toxic. For example, silicon dioxide is biocompatible, but is not biodegradable [28].
Many researchers have prepared magnetic nanoparticles covered with various surfactants or biomolecules that have been introduced directly in the synthesis process. For example, Salavati-Niasari et al. [32] have synthesized Fe3O4 nanoparticles covered with octanoic acid using a facile chemical precipitation method. The surfactant was present in the reaction system to improve dispersity. The authors have obtained magnetic nanoparticles with a size range of 25 nm. Liu et al. prepared magnetic nanoparticles coated with chitosan, for the immobilized lipase, using the co-precipitation method. They replaced water with 2% chitosan in acetic acid solution during the reaction process [33].
Atomic transfer radical polymerization (ATRP) is another common way to cover magnetic nanoparticles, developed by Wang et al. [34]. Due to the magnetic interaction of the iron oxide nanoparticles with biological fluids, the process of formation of free radicals of oxygen reactive species may be increased. To protect the environment in vivo from these toxic by-products, some materials have been used for biocompatible and rigid coatings, such as gold [28].
3. M-IONPs synthesis methods
In the past decade, numerous synthesis methods have been developed to obtain M-IONPs. On the basis that the method of preparation plays an essential role in obtaining nanoparticles with tailored properties, the research work regarding the development of new synthesis methods to control the size, shape, morphology and magnetic properties of these nanoparticles is a permanent challenge. In the same time, the synthesis method has to be environmentally friendly, simple, inexpensive and reproducible. Many scientific publications have described efficient synthesis methods, which allow the obtaining of monodisperse magnetic nanoparticles, stable for a long time with controlled shape.
The synthesis method has to ensure the obtaining of magnetic nanoparticles with specific properties to their application domain by changing the experimental reaction conditions. For biomedical applications, superparamagnetic iron oxide nanoparticles with a specific surface chemistry (for in vivo applications), high magnetization values and a narrow size distribution of the particles with size below 100 nm are needed. Magnetite (Fe3O4) and maghemite (γ-Fe2O3) have attracted particular attention because, under certain synthesis conditions, they are superparamagnetic, being also biocompatible, thus becoming the magnetic nanomaterials most commonly used in medical applications.
Hereinafter, the most popular synthesis methods used for obtaining M-IONPs will be described. After the chemical surface modification of magnetic nanoparticles by binding drugs, proteins, enzymes, antibodies, etc., they can be directed to an organ, tissue or tumor with the help of an external magnetic field. The methods described below allow to obtain magnetic nanoparticles with narrow size dimensions, desired shape and morphology, by changing the conditions and/or parameters of the synthesis. The most used and popular method for the synthesis of magnetite, being in the same time simple and efficient, is the chemical precipitation of iron salts [35–39].
3.1. Precipitation method
The first synthesis of superparamagnetic iron oxide nanoparticles was reported by Massart, and the method consists in mixing two salts of Fe3+ and Fe2+ in a molar ratio of 2:1 in aqueous medium followed by precipitation of these salts using a precipitating agent (a base – NH3) under inert atmosphere or at elevated temperature, resulting a black magnetic precipitate [40]. The equation of the chemical reaction which underlies the formation of magnetite may be written as Eq. (1):
Fe2++2Fe3++8OH−→Fe(OH)2+2Fe(OH)3→Fe3O4↓+4H2OE1
Magnetite is not stable at room temperature, being sensitive to oxidation in contact with air, easily transforming into maghemite, according to Eq. (2):
2Fe3O4+12O2→3γ−Fe2O3E2
The precipitation process is based on two steps regarding the formation of the solids [41, 42]: (i) nucleation—a very short period, occurs only when the concentration of the constituent species reaches suprasaturation and (ii) slow controlled growth of the preformed nuclei, by diffusion from the solutions to the surfaces of the crystal. To avoid the formation of polydispersed nanoparticles, it is necessary that the two stages to be separated, i.e., nucleation does not take place simultaneously with crystal growth. By controlling the two processes, monodispersed magnetic particles can be obtained. If the nuclei start to form in the same time, the growth of these nuclei leads to particles with very narrow size distribution. Therefore, the size of the obtained particles can be controlled but only in the nucleation step because the size of the particles does not change during the growth process.
It has been shown that by controlling both the pH of the reaction medium and the ionic strength, it is possible to control the mean size of the particles. Jiang et al. have demonstrated that the size of the particles has an inverse proportionality with the pH and the ionic strength of the precipitation medium [43]. These two parameters (pH and the ionic strength) also affect the chemical surface of the crystals and the electrostatic surface charge [44].
Other parameters that can influence the size, shape and composition of the magnetic iron oxide nanoparticles are the nature of iron salts (chlorides, perchlorates, nitrates, sulfates, etc.) and the molar ratio Fe3+/Fe2+. Roth and co-workers published a good analysis regarding the influence of the reaction conditions on the formation of superparamagnetic iron oxide nanoparticles. The authors demonstrated that for obtaining particles with a size between 3 and 17 nm with high saturation magnetization a higher reaction temperature, higher iron salt concentration, Fe3+/Fe2+ molar ratio below 2 and a molar ratio of hydroxide ions/iron ions of 1.4:1 are needed [45].
Wu et al. investigated the effect of the vacuum drying method on the change of the morphology and magnetic properties of magnetic iron oxide nanoparticles (M-IONPs). They revealed that the obtained nanoparticles tend to agglomerate more easily when their average diameter decreased, but the structure and morphology are maintained better by ambient air drying. They also obtained magnetic nanoparticles with high saturation magnetization after drying the obtained nanoparticles in a vacuum at 70°C [36].
The same group of researchers in another study has synthesized Fe3O4 nanoparticles by utilizing ultrasonic-assisted chemical co-precipitation. They used high purity iron separated from iron ore tailings by an acidic leaching method and obtained superparamagnetic iron oxide nanoparticles without a protecting gas [46]. Pereira and co-workers have synthesized superparamagnetic Fe3O4 nanoparticles with small particle size (4.9–6.3 nm) and improved magnetic properties by one-step aqueous precipitation route based on the use of a new type of alkaline agents [47]. The alkaline agents that they have used include alkanolamines, isopropanol amine and diisopropanolamine. The base that they have used, instead of the most used—NaOH, leads to smaller particle sizes (up to 6 times) and enhanced saturation magnetization (up to 1.3 times). Generally, the size of the particles is proportionally with the magnetization saturation, but the above results showed improved magnetic properties while keeping their small size.
Besides the many advantages of the precipitation method (high saturation magnetization, rapid synthesis with high yield, versatility, nanoparticles with the desired morphology and characteristics), it shows several disadvantages, like oxidation, magnetic nanoparticles with particle size distribution that cannot be controlled, polydispersion and weak crystallization which leads to nanoparticles with low saturation magnetization.
3.2. Thermal decomposition
Thermal decomposition of organometallic compounds in high boiling organic solutions in the presence of stabilizers is also a popular method for the synthesis of the spinel structured Fe3O4 and a very promising technique for obtaining high-quality superparamagnetic iron oxide nanoparticles. The magnetic nanoparticles obtained by this method proved to be superior to those obtained by precipitation, because the nucleation process can be separated by the growth process and the hydrolysis reaction is avoided [48].
The method is based on the decomposition of an iron precursor at high temperature in the presence of solvents which contain stabilizing surfactants (such as oleic acid or oleylamine) [49–51]. By varying the reaction mixtures and modifying the synthesis condition, it can be obtained M-IONPs with controlled size, size distribution and composition. The most commonly used precursors employed to prepare monodispersed M-IONPs with diameter ranging from 3 to 50 nm are of the form: (I) metal acetylacetonate—[M(acac)n] (where M = Fe, Co, Ni, Mn, Cr; n = 2 or 3) [52]; (II) metal cupferronates—[Mx(cup)x] (where cup = N-nitrosophenylhydroxylamine); (III) metal oxalate—[M(C2O4)n•2H2O]; (IV) metal carbonyl—Fe3(CO)12 [53] or Fe(CO)5 [50]; (V) metal acetate—[M(CH3COO)n]; (VI) metal carboxylate, (VII) metal-urea complex—[Fe(CON2H4)6](NO3)3 [54]; (VIII) Prussian Blue—Fe4[Fe(CN)6•14H2O] [55, 56]; (IX) metal chloride and (X) ferrocene—Fe(C2H5)2 [57].
Using the thermal decomposition method, it can be easy to control the size and morphology of magnetic nanoparticles by controlling the ratio of the starting reagents, i.e. the ratio between the organometallic compounds, surfactant and solvent. Reaction time, temperature and aging period are equally important for the control of size and morphology. Hyeon obtained monodispersed iron oxide nanoparticles with size range from 4 to 20 nm by thermal decomposition of Fe(CO)5 in the presence of oleic acid at 100°C. Initially, he obtained an iron-oleic acid complex, which was leaved to aging at high temperature (300°C) [50].
Pérez-Mirabet et al. used oleylamine both as stabilization agent (for the stabilization of the particles in solution) and as capping ligand (for the control of particles size), respectively, by one-pot thermal decomposition of Fe(acac)3 and M(acac)2 (M = Co, Mn, Cu and Zn) in oleylamine. They obtained magnetic spinel ferrite nanoparticles with average size of 12 nm and a saturation magnetization Ms = 76 emu/g, very close to the bulk magnetite (92 emu/g) [58].
This method is also suitable for synthesis of nanocubes and nanospheres, which are magnetic nanoparticles as well. Amara et al. synthesized Fe3O4 nanocubes and nanospheres by a new simple and single-step process [59]. They used various mixtures of ferrocene and polyvinylpyrrolidone (PVP) by solventless thermal decomposition. Lynch et al. obtained magnetic colloidal iron oxide nanoparticles by thermal decomposition. They generated gas bubbles (Ar) by boiling solvents. Their results illustrated that the argon bubbles had a stronger effect on the nucleation process of magnetic iron oxide nanoparticles than on their growth process [60]. Due to the nucleation process that involves boiling solvents, most often the accurate shape of the magnetic iron oxide nanoparticles is not fully reproducible using the thermal decomposition method.
3.3. Microemulsion method
A microemulsion is formed when a colloidal substance is dispersed in a solvent, that is not compatible with the substance (e.g. water and oil), through a surfactant. Finally, a microemulsion must be clear and stable, as long as it is an isotropic mixture of oil, water and surfactant. The surfactant forms a monolayer film at the oil/water interface, in which the hydrophilic head groups of the surfactant are dissolved in oil phase (consisting of a mixture of hydrocarbons and olefins) and the hydrophobic tail of the surfactant in the aqueous phase (consisting of metal salts) and vice versa, depending on the used surfactant. There are known two types of microemulsion: direct microemulsion, when the oil is dispersed in water and reversed microemulsion, when the water is dispersed in oil. Both have been used to synthesize the magnetic iron oxide nanoparticles with tailored size and shape. The most common surfactants that are widely used in the fabrication of M-IONPs by microemulsion method are bis(2-ethylhexyl) sulfosuccinate (AOT), sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and poly-vinylpyrrolidone (PVP). Throughout time, the microemulsion method proved to be a simple and versatile method for fabrication of nanosized magnetic nanoparticles [61–65].
According to the literature, the size of the resulted nanoparticles can be controlled if the surfactant is proper chose and also by varying the ratio of water/oil/surfactant, the initial concentration of the reactants and the droplet size and by controlling the reaction temperature and time [66, 67]. The size of the synthesized nanoparticles can also be controlled in suitable narrow range by carrying out the reaction in nanoreactor [62, 64, 67].
Lu et al. demonstrated that the surfactant nature has an important role on the final properties of the nanoparticles [64]. The authors have investigated the effect of SDS (anionic surfactant), DTAB and CTAB (cationic surfactants) and non-ionic surfactant on the preformed crystal, on stoichiometric situations and on the magnetic properties of the resulted Fe3O4 nanoparticles. In all the cases, the authors have obtained Fe3O4 nanoparticles with size less than 16 nm, but in the case of using the cationic surfactants also obtained a good saturation magnetization, which is an essential parameter for biological applications.
Okoli et al. have prepared M-IONPs by the two types of microemulsion (water/oil and oil/water), to be used in binding and separation of proteins. The authors demonstrated that by using a water/oil microemulsion, it can obtain magnetic iron oxide nanoparticles with a surface area of 147 m2/g compared to 304 m2/g for the magnetic nanoparticles obtained by oil/water microemulsion [68, 69]. The M-IONPs specific surface area is inversely proportional with the size of nanoparticles, the higher is the specific surface area the smaller nanoparticles size is obtained.
The advantage of this method is the fact that it can be obtain magnetic nanoparticles with uniform morphology and controllable size; but the major drawbacks are the requirements of a large amount of solvent and the excess of surfactant that has to be eliminated.
3.4. Hydrothermal and solvothermal methods
In case of these methods, the reaction takes place in aqueous medium (the hydrothermal method) or in organic medium (solvothermal method), in reactors or autoclaves, at temperatures between 130 and 250°C under high vapor pressure, in the range 0.3–4 MPa [70–72]. Using this method, it can be obtained magnetic iron oxide nanoparticles with tailored properties (size and shape) by tuning the reaction conditions. The hydrothermal method is known as an environment-friendly process for the obtaining of M-IONPs, due to the raw materials used such as sulfates and chlorides—as cation source, dissolved in water [73].
Lin et al. [74] has used hydrothermal and solvothermal methods to obtain hollow M-IONPs. Briefly, they used FeCl3 (as source of iron), ethylene glycol (as reducing agent), ammonium acetate and urea were used to guide the formation of hollow magnetite spheres. After homogeneous dispersion, the mixture is transferred to a Teflon-lined stainless steel autoclave and sealed to heat at about 200°C for 8–24 h. The authors demonstrated that the Fe3+ ions on the surface of the hollow spheres exist in the form of Fe3O4, and the results are confirmed by the Mössbauer measurements. Tian et al. synthesized ultra-small monodisperse Fe3O4 nanoparticles, with precise size control of 1 nm, by solvothermal method [75]. They used Fe(acac)3 as iron source, n-octanol as a solvent and n-octylamine as a reductant. The authors obtained Fe3O4 nanoparticles with a size range from 4 to 6 nm, by varying the volume ratios of n-octylamine and n-octanol, without the need of a gas (N2) bubbling or reflux conditions. By comparing this method with the thermal decomposition methods for obtaining Fe3O4 nanoparticles, this solvothermal process was more convenient.
Stoia et al. [14] synthesized FexOy and FexOy/C nanocomposite by solvothermal method, with the purpose of using these nanocomposites as adsorbents for methylene blue removal from aqueous solutions. The authors used FeCl3 as iron source, 1,2-propanediol as solvent and diethylamine as precipitating agent. The activated carbon was introduced into system in order to obtain homogenous FexOy/C composites with high specific surface area and magnetic properties. Some researchers have attempted to modify the hydrothermal process. Ahmadi et al. obtained Fe3O4 nanoparticles at low temperature (140°C) without having to autoclave. They have studied kinetics of the reaction, but the magnetic properties of the resulted nanoparticles are inadequate in short reaction time (below 2 hours) [76].
As advantages, the hydrothermal and solvothermal methods are suitable for obtaining shape-controlled M-IONPs. As a disadvantage, in the case of hydrothermal technique, the reaction takes place for a long time and the amounts of resulting products are low [76].
3.5. Combustion method
The combustion method is an alternative to the currently used methods, being barely mentioned in the literature for the synthesis of M-IONPs. The combustion method have a lot of advantages due to the simplicity of the working technique, short reaction time and low energy consumption, being in the same time environmentally friendly.
The combustion method involves the strong exothermic redox reaction between an oxidizing agent (iron nitrate) and various reducing agents (fuels) of organic nature. The initiation of the combustion process takes place by rapidly heating the mixture of raw materials at relatively low temperatures below 500°C (Figure 4). The reaction stoichiometry has a decisive role in the characteristics of the reaction product, especially in the granule size, since a combustion reaction does not occur for any molar fuel/oxidizing agent ratio.
Figure 4.
The general scheme for obtaining iron oxide magnetic powders using the combustion method.
The use of metallic nitrates in a mixture with a suitable fuel has the great advantage that, following the combustion reaction, the gases are released without a high risk of toxicity: CO2, N2 and H2O [77]. By using a proper fuel, proper auxiliary additives, as well as an appropriate oxidizing agent/fuel ratio, it can be tailored the size of the particles, the specific surface area and the crystallinity degree of the obtained material [78, 79].
Ianoş et al. reported a new combustion synthesis technique for the preparation of nanosized Fe3O4 nanoparticles [80]. The authors developed a new, facile and cheap scheme of installation for combustion synthesis of Fe3O4 nanoparticles in the absence of air. They also investigated the effect of both the reaction atmosphere (in the presence or in the absence of air) and the fuels nature on the properties of the resulted nanoparticles. Using sucrose, citric acid and glucose as fuels, the authors demonstrated that the reaction atmosphere is very important for obtaining Fe3O4 nanoparticles as a single crystalline phase. There were obtained Fe3O4 nanoparticles in the size range of 10 (when glucose was used as fuel) to 18 nm (when citric acid was used as fuel).
Mihoc et al. also investigated the effect of both the fuels nature and the reaction atmosphere for obtaining magnetic nanoparticles used as adsorbent for the removal of phenol and p-chlorophenol from wastewater [81]. The authors revealed that the working atmosphere influences the phase composition of the combustion reaction product. Using urea with ammonium chloride as fuels, the final product of reaction was α-Fe2O3 (when the reaction took place in air). Working in the absence of air, using oxalic, tartaric and citric acid as fuel, the single phase resulted in combustion reaction was Fe3O4, irrespective of the nature of the fuel.
Using the combustion method, the magnetic oxide nanoparticles are covered with some organic residues resulting from fuel combustion. Mihoc et al. demonstrated that these materials exhibit better adsorption capacity as compared with the naked magnetic oxides [82].
However, if it is desired to remove the residual carbon resulting from the combustion process, Ianos et al. found a method in which the residual carbon was eliminated by washing the magnetic nanoparticles several times with H2O2. They revealed that by combustion reaction between Fe(NO3)3•9H2O and C6H12O6 a black magnetic nanoparticle containing γ-Fe2O3 and residual carbon was obtained. The authors demonstrated that by H2O2 treatment of the resulted magnetic nanoparticles the carbon was removed by chemical oxidation, from 32.7 to 0.4%, and the color of the sample changed from black to reddish brown [83].
M-IONPs proved to be versatile due to the large range board of applications in medicine. Nanomedicine is an emerging field that offers new approaches but especially new solutions for many medical problems. For example, the discovery of antibiotics has been of historic importance, but over time, antibiotic resistance has become an issue and new approaches are therefore needed. Many groups of researchers have already demonstrated that the synergic effects of the antimicrobials agents (not only the antibiotics) with nanoparticles can be promoted as a new method for the severe infection treatments, even with low antimicrobial doses.
For the biomedical uses, only the M-IONPs which fulfill the following requirements are proper: superparamagnetic properties at room temperature, large saturation of magnetizations, biocompatibility and sizes around 20 nm for in vivo administration. To convert the pure magnetic nanoparticles in biocompatible colloidal suspensions, many researchers have proposed the use of different polymers like covering agents or surfactants like starch, heparin, chitosan, dextran, oleic acid, polyethylene glycol (PEG), etc.
Polymer coating can be accomplished during or after the synthesis of magnetic nanoparticles. Polyethylene glycol (PEG) is a water-soluble, biocompatible hydrophilic polymer that can be used successfully in the synthesis of biocompatible nanoparticles with increased resistance to blood circulation [84]. Another alternative to covered magnetic nanoparticles is the use of copolymers that produce core-shell nanoparticles with possible applications in drug transport (drug vector) [85].
The use of inorganic compounds such as gold, silver, silica gel and carbon as surfactants not only provides good stability to the nanoparticles but also allows functionalizing their surface by grafting certain biological ligands. Covering of magnetic nanoparticles with gold seems to be ideal because of its low reactivity; however, coating the magnetic nanoparticles directly with gold is very difficult due to the different nature of the two surfaces [86–89]. The silica gel is the most widely used compound in the preparation of functionalized iron oxide nanoparticles surface, because it has several advantages: excellent biocompatibility, hydrophilicity, the feasibility of integrating other functional groups on the surface due to terminal silanol groups that can react with different coupling agents, provides good stabilization of the magnetic iron oxide nanoparticles in the solution, prevents the interaction between the nanoparticles thus preventing the agglomeration of the particles over time and ensures better encapsulation [90]. A very good coating of carbon layers provides an effective barrier against oxidation and acidic erosion of magnetic nanoparticles. It is therefore possible to synthesize carbon-coated magnetic nanoparticles that are thermally stable, biocompatible and also have high oxidation stability, which is crucial for certain applications [89].
4. In vitro biological impact
4.1. Magnetic iron oxide nanoparticle effect on normal cells
Iron ions play major biological roles in different physiological processes, including DNA synthesis, oxygen transport, mitochondrial respiration, heme synthesis, and in metabolic functions at central nervous system level (nitric oxide metabolism, oxidative phosphorylation and myelin and neurotransmitter synthesis). Moreover, iron proved to be an essential factor for an appropriate function of neurons by acting as cofactor for tyrosine hydroxylase, an enzyme with a critical role in dopamine synthesis and the viability of neural cells. A dysregulation of the iron homeostasis or transport leads to unbalanced physiological functions and cytotoxic reactions. The free intracellular Fe2+ ions react with hydrogen peroxide (H2O2) and determine the generation of reactive oxygen species (ROS), process known as Fenton reaction. An increased ROS concentration activates a cascade of events (release of iron ions into the cytosol by inducing an augmented permeability of the outer mitochondrial membrane and detrimental effects on lysosomal membrane; lipid peroxidation, damaged proteins, break of DNA chains and degradation of bases, mutations, deletions or translocations at nuclear level) that has as endpoint cell death. The pathologies that are associated with this type of cellular damage are aging, cancer and neurodegenerative diseases [91]. Another mechanism of inducing cell death by the iron ions is the apoptotic pathway via mitochondria, as follows: a high amount of iron ions into the mitochondria determine the opening of the mitochondrial transition pore, release of Ca2+ and cytochrome c and activation of apoptotic cascade [91, 92].
Based on these data, concerning the toxicity induced by iron ions, it is imperative to study the possible toxic effects induced by M-IONPs, mainly since these particles present a higher reactivity as compared with the normal sized ones. The magnetic character of iron oxide nanoparticles offers some advantages, including the capacity of this nanosized compounds to be driven to targeted sites by an external magnetic field, even to tissues and organs that are difficult to reach in normal conditions (blood brain barrier and central nervous system). M-IONPs penetrate into the cells via receptor-mediated endocytosis and settle into the lysosomes, organelles characterized by the presence of an acidic medium, where it takes place the metabolization of the nanoparticles and free iron ions are released into the cell [91].
In a previous study, it was demonstrated that M-IONPs penetrate differentially into the neural cells (glial cells, primary neurons of the cerebellum, microglia, astrocytes, oligodendrocytes and Schwann cells), based on their dimensions: large size nanoparticles were absorbed by endocytosis, whereas small sized ones via pinocytosis [91, 93]. It was also proved that exposure to M-IONPs has an impact on iron homeostasis by upregulating the proteins responsible for iron storage or export from the cell and by downregulating the proteins expression involved in iron uptake [94].
Besides these positive features, application of an external magnetic field leads to accumulation of M-IONPs in target cells and potential toxicity. The accumulation of iron into the cells after exposure to M-IONPs seems to be dependent on several factors, such as (i) concentration and dose of M-IONPs (high concentrations require a longer period for elimination—several months, whereas M-IONPs in low concentrations can be eliminated within 3 weeks), size (small size nanoparticles cumulate in increased concentrations as compared to large size nanoparticles), shape (spherical nanoparticles present a longer degradation process due to a small contact surface), coating (some coating agents may prolong the degradation process or may increase it), the functional groups (the positively charged functional groups present in M-IONPs structure increase their uptake by the cells) and cell type (microglia have a higher affinity for M-IONPs, whereas into the brain endothelial cells penetrate less nanoparticles) [91].
A significant number of studies sustained that M-IONPs exerted in vitro and in vivo toxicity. The main players responsible for toxic effects are considered to be the iron ions released from M-IONPs at lysosomal level, which react with hydrogen peroxide and lead to ROS generation [91]. Exposure of neural cells to M-IONPs was associated with a low concentration of ROS, but a reduced level of glutathione and mitochondrial membrane hyperpolarization [95]. Other studies conducted on healthy cell lines (both human and animal origin) pointed out that bare M-IONPs may induce cytotoxic effects via ROS generation, leading to cell death [96–98].
The oxidation state of iron (Fe2+ or Fe3+) plays a major role in determining the nanoparticles toxicity according to the studies that affirm that Fe3+ in Fe2O3 is more toxic than Fe2+ in Fe3O4 and causes more DNA oxidation [91, 99].
The concentration of M-IONPs is also important in the assessment of M-IONPs toxicity. In one of our previous studies developed on HaCat cells (human keratinocytes), it was shown that concentrations lower than 25 μg/mL did not induce toxicity in terms of viability and cytoskeleton changes (Figure 5) [100].
Figure 5.
The impact of magnetite and maghemite obtained by combustion method on HaCat cell morphology after 24 h stimulation.
Shelat and coworkers indicated a dose-dependent cytotoxic effect of M-IONPs on mouse embryonic fibroblast (NIH 3 T3) [101]. It was also assessed the effect of negatively charged superparamagnetic iron oxide nanoparticles on heart cells and no changes in actin cytoskeleton were observed, whereas in the case of brain and kidney cells, a disruption of the actin cytoskeleton was detected, but some increased vascular permeability was seen after exposure [102].
Another sign of toxicity that was described after neural cells exposure to M-IONPs was represented by protein aggregation. In addition, it was shown that M-IONPs induce apoptosis of hepatocytes in a mitochondrial-dependent way consisting of upregulation of pro-apoptotic markers (Bax and Bad) and downregulation of bcl-2 (anti-apoptotic); decrease of mitochondrial membrane potential followed by the release of cytochrome c into the cytosol what leads to activation of caspases cascade and apoptosis induction (Figure 6) [91].
Figure 6.
Mechanisms of toxicity induced by M-IONPs to normal cells (neural cells and hepatocytes): oxidative stress and apoptosis.
Based on the data that were presented in this section, it could be said that the mechanisms involved in M-IONPs toxicity are accumulation of iron ions, oxidative damage by generating reactive oxygen species, protein aggregation and apoptosis.
Mutagenic effects of M-IONPs on different murine and mammalian normal cell lines were clearly synthesized in an extensive review [103].
4.2. Magnetic iron oxide nanoparticles effect on cancer cells
SPIONs (superparamagnetic iron oxide nanoparticles) are the most frequently used iron oxide nanoparticles in the biomedical applications due to their proper size (range between 50 and 200 nm) and the magnetic properties responsible for the lack of particle aggregates in vivo. Another type of iron oxide nanoparticles is represented by USPIONs (ultra-small superparamagnetic iron oxide nanoparticles), which have a diameter lower than 50 nm. The mandatory features of M-IONPs that must be analyzed in order to establish the bioavailability and the possible interactions with endogenous compounds (proteins, immune system cells, etc.) are: (i) size (the recommendable size for biomedical applications is between 10 and 200 nm; the ones that are too big will be assimilated by liver and spleen cells, the ones that are too small will be filtrated by the kidneys and their life in the bloodstream is reduced); (ii) superparamagnetism and (iii) presence of a coating agent [104].
The affinity of liver, spleen, bone marrow and lymph nodes for SPIONs after their removal from the blood by the mononuclear phagocytic system (MPS) after intravenous administration represents the reason for the study of this type of nanoparticles as contrast agents but also for their use as delivery tools for chemotherapeutic agents. USPIONs due to their small size possess the capacity to escape macrophages of MPS surveillance and their circulation time is higher, but they also encounter macrophages in deeper compartments.
The changes concerning the surface of the nanoparticles by using a coating agent proved to exert multiple roles: to improve colloids stability, to enhance the bioavailability and the bloodstream half-life and to reduce precipitation and formation of conglomerates [104, 105]. M-IONPs were used as drug delivery agents and as contrast agents based on their potential to activate at cellular and molecular levels [105].
Due to the multiple applications of M-IONPs in biomedical fields (drug delivery, as contrast agents, hyperthermia treatment), it was also verified the effects of the hollow nanoparticles (without payload) on different tumor cell lines.
As mentioned in the previous section, M-IONPs mediate DNA lesions in normal cells, and this property is also exerted in the case of tumor cells. The effect observed was dose-dependent and time-dependent and consisted of damage of tail length and DNA strand breaks. The results were similar in all the tumor cell lines tested: human breast cancer cell line (MCF-7), human fibrosarcoma cells, lung cancer and cervix carcinoma cells [103].
Another mechanism of M-IONPs by which are able to harm cancer cells is represented by the ability to induce magnetic hyperthermia in the form of heat generated by the release of energy after applying a high-frequency alternating magnetic field. The principle of action of this technique consists in raising the cell temperature abnormally to 41–45°C, which leads to significant detrimental effects that can be reversible in the case of normal cells whereas irreversible for cancer cells [105].
A novel proposed mechanism for M-IONPs-induced cell death is enucleation described by Paunescu and coworkers, process observed after exposure of breast cancer cells (MCF-7) and human melanoma (SK-BR-3) to magnetic iron oxide nanoparticles obtained by combustion synthesis [106]. The enucleation phenomena is well described for erythroid terminal differentiation process and there is also used a term in the literature “enucleation sign” that is specific for enhanced computed tomographic images of the ruptured hepatocellular carcinoma. The definition for this term is “the separation of tumor content with intraperitoneal rupture into the perihepatic space, which is seen as low attenuating lesion from peripheral enhancing rim on arterial phase imaging” [107]. The process observed by Paunescu et al. was described as a non-physiological process and it was unrelated with the process described for erythroblast enucleation [106].
The M-IONPs proved a cytotoxic effect against murine melanoma cells B16, cytotoxicity evaluated by the means of MTT viability assay [108].
Other mechanisms of action as anticancer agents may be attributed to M-IONPs, mechanisms that are related with the effects induced by the chemotherapeutical agents loaded in the engineered nanoparticles. The large surface-to-volume ratio characteristic for M-IONPs make them suitable to adsorb proteins or load drugs and attractive for in vivo applications, such as MRI, drug and gene delivery, cancer treatment, hard tissue repair and tissue engineering and biosensors [105].
Recent studies mention the use of M-IONPs as improved contrast agents in the diagnosis of cardiovascular pathologies, mainly in atherosclerosis for detection of unstable plaques by the means of MRI (magnetic resonance imaging) [104]. The commercial products based on M-IONPs applied as contrast agents in MRI are: Ferumoxytol (Feraheme—detection of primary tumors and cancer lymph node metastasis), Ferumoxides (Feridex—detection of liver lesions), Ferucarbotran (Resovist—detection of small focal liver lesions), Ferumoxtran—10 (Combidex or Sinerem—detection of metastatic disease in lymph nodes), etc. [104]. Some of these products are included in clinical trials for additional effects, such as Endorem—for tracking monocytes and inflammation cells, Feridex—to keep track of adult bone marrow-derived stromal cells for severe cases of Multiple Sclerosis therapy and Supravist (ferucarbotran—small size nanoparticles)—as enhancing blood pool agent [104, 109].
5. Concluding remarks
The intrinsic magnetic properties, the biocompatibility and biodegradability and the capacity to respond to an external magnetic field are unique features that recommend magnetic iron oxide nanoparticles as promising nanomaterials in biomedical applications. The recent advances in this field led to the synthesis of engineered and targeted M-IONPs that might be successfully applied for smart therapies, including controlled drug release, hyperthermia treatment, magnetofection and gene delivery, mapping of lymph nodes and tissue engineering. M-IONPs could be considered theranostics tools based on their capacity to combine their use in diagnostic, treatment and follow-up of a pathology. Despite all these beneficial effects, an important matter should be taken into consideration when M-IONPs are administered in vivo, this matter consisting in the thorough analysis of the factors that might induce toxic reactions like size, charge, coating agent, functional groups and shape. There are still some challenges to achieve M-IONPs optimum efficacy and safety, but the existent drawbacks can be corrected by the improvement of their properties by the means of appropriate methods, further studies and inclusion in clinical trials.
Acknowledgments
This work was supported by a grant of Minister of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P4-ID-PCE-2016-0765, within PNCDI III.
\n',keywords:"magnetic iron oxide nanoparticles (M-IONPs), cancer, enucleation, apoptosis, magnetite, maghemite, combustion method",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/60330.pdf",chapterXML:"https://mts.intechopen.com/source/xml/60330.xml",downloadPdfUrl:"/chapter/pdf-download/60330",previewPdfUrl:"/chapter/pdf-preview/60330",totalDownloads:730,totalViews:409,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:0,dateSubmitted:"July 20th 2017",dateReviewed:"January 18th 2018",datePrePublished:null,datePublished:"July 11th 2018",dateFinished:null,readingETA:"0",abstract:"The broad area of magnetic iron oxide nanoparticle (M-IONP) applications and their exclusive physico-chemical characteristics (superparamagnetic properties per se, solubility and stability in aqueous solutions, and high bioavailability in vivo) make these nanoparticles suitable candidates for biomedical uses. The most employed magnetic iron oxides in the biomedical field are magnetite and maghemite. Cancer represents a complex pathology that implies multiple mechanisms and signaling pathways, this complexity being responsible for the increased resistance to therapy and the lack of an effective curative treatment. A potential useful alternative was considered to be the use of magnetic iron nanoparticles. The M-IONPs proved to be effective as contrast agents in magnetic resonance imaging, as drug delivery carriers for different therapeutic agents, in magnetic cell separation assays, and are suitable to be engineered in terms of size, targeted delivery and substance release. Moreover, their in vivo administration was considered safe, and recent studies indicated their efficiency as anticancer agents. This chapter aims to furnish an overview regarding the physico-chemical properties of M-IONPs (mainly magnetite, maghemite and hematite), the synthesis methods and their in vitro biological impact on healthy and cancer cell lines, by describing their potential mechanism of action—enucleation, apoptosis or other mechanisms.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/60330",risUrl:"/chapter/ris/60330",book:{slug:"iron-ores-and-iron-oxide-materials"},signatures:"Elena-Alina Moacă, Elena Dorina Coricovac, Codruta Marinela\nSoica, Iulia Andreea Pinzaru, Cornelia Silvia Păcurariu and Cristina\nAdriana Dehelean",authors:[{id:"141027",title:"Dr.",name:"Cristina",middleName:null,surname:"Dehelean",fullName:"Cristina Dehelean",slug:"cristina-dehelean",email:"cadehelean@umft.ro",position:null,institution:null},{id:"173283",title:"Dr.",name:"Dorina",middleName:null,surname:"Coricovac",fullName:"Dorina Coricovac",slug:"dorina-coricovac",email:"dorinacoricovac@umft.ro",position:null,institution:null},{id:"186678",title:"Dr.",name:"Codruta",middleName:null,surname:"Soica",fullName:"Codruta Soica",slug:"codruta-soica",email:"codrutasoica@umft.ro",position:null,institution:null},{id:"217849",title:"Associate Prof.",name:"Iulia Andreea",middleName:null,surname:"Pinzaru",fullName:"Iulia Andreea Pinzaru",slug:"iulia-andreea-pinzaru",email:"iuliapinzaru@umft.ro",position:null,institution:null},{id:"219727",title:"Mrs.",name:"Elena Alina",middleName:null,surname:"Moaca",fullName:"Elena Alina Moaca",slug:"elena-alina-moaca",email:"alina.moaca@umft.ro",position:null,institution:null},{id:"219728",title:"Prof.",name:"Cornelia Silvia",middleName:null,surname:"Pacurariu",fullName:"Cornelia Silvia Pacurariu",slug:"cornelia-silvia-pacurariu",email:"cornelia.pacurariu@upt.ro",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Properties of magnetic nanoparticles",level:"1"},{id:"sec_2_2",title:"2.1. Magnetic behavior",level:"2"},{id:"sec_3_2",title:"2.2. Size",level:"2"},{id:"sec_4_2",title:"2.3. Charge",level:"2"},{id:"sec_5_2",title:"2.4. Surface functionality and colloidal stability",level:"2"},{id:"sec_7",title:"3. M-IONPs synthesis methods",level:"1"},{id:"sec_7_2",title:"3.1. Precipitation method",level:"2"},{id:"sec_8_2",title:"3.2. Thermal decomposition",level:"2"},{id:"sec_9_2",title:"3.3. Microemulsion method",level:"2"},{id:"sec_10_2",title:"3.4. Hydrothermal and solvothermal methods",level:"2"},{id:"sec_11_2",title:"3.5. Combustion method",level:"2"},{id:"sec_13",title:"4. In vitro biological impact",level:"1"},{id:"sec_13_2",title:"4.1. Magnetic iron oxide nanoparticle effect on normal cells",level:"2"},{id:"sec_14_2",title:"4.2. Magnetic iron oxide nanoparticles effect on cancer cells",level:"2"},{id:"sec_16",title:"5. Concluding remarks",level:"1"},{id:"sec_17",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Reddy LH et al. Magnetic nanoparticles: Design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chemical Reviews. 2012;112:5818-5878'},{id:"B2",body:'Colombo M et al. Biological applications of magnetic nanoparticles. Chemical Society Reviews. 2012;41:4306-4334'},{id:"B3",body:'Shete PB et al. Water dispersible oleic acid-coated Fe3O4 nanoparticles for biomedical applications. Journal of Magnetism and Magnetic Materials. 2015;377:406-410'},{id:"B4",body:'Bica D. Preparation of magnetic fluids for various applications. Romanian Reports in Physics. 1995;47(3-5):265-272'},{id:"B5",body:'Mahmoudi H, Jafari AA. Facial preparation of sulfonic acid-functionalized magnetite-coated maghemite as a magnetically separable catalyst for pyrrole synthesis. ChemCatChem. 2013;5:3743-3749'},{id:"B6",body:'Wang YM et al. Synthesis of Fe3O4 magnetic fluid used for magnetic resonance imaging and hyperthermia. Journal of Magnetism and Magnetic Materials. 2011;323:2953-2959'},{id:"B7",body:'Cho M et al. Assembly of iron oxide nanocubes for enhanced cancer hyperthermia and magnetic resonance imaging. Nanomaterials. 2017;7(72):1-12'},{id:"B8",body:'Estelrich J et al. Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery. International Journal of Molecular Sciences. 2015;16:8070-8101'},{id:"B9",body:'Lee JY et al. Low-density lipoprotein-mimicking nanoparticles for tumor-targeted theranostic applications. Small. 2015;11:222-231'},{id:"B10",body:'Hola K et al. Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances. Biotechnology Advances. 2015;33(6-2):1162-1176'},{id:"B11",body:'Păcurariu C et al. Synthesis and characterization of gamma-Fe2O3/SiO2 composites as possible candidates for magnetic paper manufacture. Ceramics International. 2015;41(1):1079-1085'},{id:"B12",body:'Gao D et al. Preparation and characterization of a new white magnetic paper. Materials Letters. 2014;137:487-490'},{id:"B13",body:'Tang L et al. Synergistic adsorption and reduction of hexavalent chromium using highly uniform polyaniline-magnetic mesoporous silica composite. Chemical Engineering Journal. 2014;254:302-312'},{id:"B14",body:'Stoia M et al. Solvothermal synthesis of magnetic FexOy/C nanocomposites used as adsorbents for the removal of methylene blue from wastewater. Journal of Thermal Analysis and Calorimetry. 2015;121:989-1001'},{id:"B15",body:'Shen X et al. One-step synthesis of water-dispersible cysteine functionalized magnetic Fe3O4 nanoparticles for mercury (II) removal from aqueous solutions. Applied Surface Science. 2014;317:1028-1034'},{id:"B16",body:'Majewski P, Thierry B. Functionalized magnetite nanoparticles—Synthesis, properties, and bio-applications. Critical Reviews in Solid State and Materials Sciences. 2007;32(3-4):203-215'},{id:"B17",body:'Collingwood JF, Telling ND. Chapter 7 – Iron oxides in the human brain. In: Faivre D, editor. Iron Oxides from Nature to Applications. Germany: Wiley-VCH; 2016. p. 143'},{id:"B18",body:'Crespo RG et al. Vacancy ordering and electronic structure of γ-Fe2O3 (maghemite): A theoretical investigation. Journal of Physics Condensed Matter. 2010;22(25):255401'},{id:"B19",body:'Cuenca JA et al. Study of the magnetite to maghemite transition using microwave permittivity and permeability measurements. Journal of Physics Condensed Matter. 2016;28(10):106002'},{id:"B20",body:'Woo K, Lee HJ. Synthesis and magnetism of hematite and maghemite nanoparticles. Journal of Magnetism and Magnetic Materials. 2004;272:1155'},{id:"B21",body:'Genuzio F et al. Phase transformations in thin iron oxide films: Spectromicroscopic study of velocity and shape of the reaction fronts. Surface Science. 2016;648:177-187'},{id:"B22",body:'Cornell RM, Schwertmann U. Chapter 2 – Crystal structure, In: The Iron Oxides: Structure, Properties, Reactions, Occurrences and Uses, 2nd ed., Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2003. p. 9'},{id:"B23",body:'Issa B et al. Magnetic nanoparticles: Surface effects and properties related to biomedicine applications. International Journal of Molecular Sciences. 2013;14(11):21266-21305'},{id:"B24",body:'Kuncser V et al. Chapter 7 – Engineering magnetic properties of nanostructures via size effects and interphase interactions. In: Kuncser V, Miu L, editors. Size Effects in Nanostructures: Basic and Applications. Berlin Heidelberg: Springer-Verlag; 2014. p. 169'},{id:"B25",body:'Krishnan KM. Biomedical nanomagnetics: A spin through possibilities in imaging, diagnostics, and therapy. IEEE Transactions on Magnetics. 2010;46(7):2523-2558'},{id:"B26",body:'Tombácz E et al. Magnetic iron oxide nanoparticles: Recent trends in design and synthesis of magnetoresponsive nanosystems. Biochemical and Biophysical Research Communications. 2015;468(3):442-453'},{id:"B27",body:'O\'Mahony JJ et al. Synthesis of superparamagnetic particles with tunable morphologies: The role of nanoparticle-nanoparticle interactions. Langmuir. 2013;29(8):2546-2553'},{id:"B28",body:'Mahmoudi M et al. Superparamagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy. Advanced Drug Delivery Reviews. 2011;63(1-2):24-46'},{id:"B29",body:'Osaka T et al. Effect of surface charge of magnetite nanoparticles on their internalization into breast cancer and umbilical vein endothelial cells. Colloids and Surfaces. B, Biointerfaces. 2009;71(2):325-330'},{id:"B30",body:'Cornell RM, Schwertmann U. Chapter 14 – Transformation. In: The Iron Oxides: Structure, Properties, Reactions, Occurrences and Uses. 2nd ed. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2003. p. 365'},{id:"B31",body:'Peng XH et al. Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy. International Journal of Nanomedicine. 2008;3(3):311-321'},{id:"B32",body:'Salavati-Niasari M et al. Easy synthesis of magnetite nanocrystals via coprecipitation method. Journal of Cluster Science. 2012;23:597'},{id:"B33",body:'Liu Y et al. Studies of Fe3O4-chitosan nanoparticles prepared by co-precipitation under the magnetic field for lipase immobilization. Catalysis Communications. 2011;12:717'},{id:"B34",body:'Wang Y et al. Solvent-free atom transfer radical polymerization in the synthesis of Fe2O3@polystyrene core−shell nanoparticles. Nano Letters. 2003;3(6):789-793'},{id:"B35",body:'Sun YK et al. Synthesis of nanometer-size maghemite particles from magnetite. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2004;245:15-19'},{id:"B36",body:'Wu W et al. Preparation and characterization of magnetite Fe3O4 nanopowders. Rare Metal Materials and Engineering. 2007;36(3):238-243'},{id:"B37",body:'Martinez-Mera I et al. Synthesis of magnetite (Fe3O4) nanoparticles without surfactants at room temperature. Materials Letters. 2007;61:4447-4451'},{id:"B38",body:'Hui C et al. Large-scale Fe3O4 nanoparticles soluble in water synthesized by a facile method. The Journal of Physical Chemistry. B. 2008;112(30):11336-11339'},{id:"B39",body:'Khalil MI. Co-precipitation in aqueous solution synthesis of magnetite nanoparticles using iron (III) salts as precursors. Arabian Journal of Chemistry. 2015;8(2):279-284'},{id:"B40",body:'Massart R. Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Transactions on Magnetics. 1981;17(2):1247-1248'},{id:"B41",body:'Baumgartner J et al. Nucleation and growth of magnetite from solution. Nature Materials. 2013;12(4):310-314. DOI: 10.1038/nmat3558'},{id:"B42",body:'Thanh NTK et al. Mechanisms of nucleation and growth of nanoparticles in solution. Chemical Reviews. 2014;114:7610-7630'},{id:"B43",body:'Jiang WQ et al. Preparation and properties of superparamagnetic nanoparticles with narrow size distribution and biocompatible. Journal of Magnetism and Magnetic Materials. 2004;283(2-3):210-214'},{id:"B44",body:'Tartaj P, et al. Synthesis, properties and biomedical applications of magnetic nanoparticles. In: Handbook of Magnetic Materials. Amsterdam: Elsevier; 2006. p. 403'},{id:"B45",body:'Roth HC et al. Influencing factors in the co-precipitation process of superparamagnetic iron oxide nanoparticles: A model based study. Journal of Magnetism and Magnetic Materials. 2015;377:81-89'},{id:"B46",body:'Wu S et al. Fe3O4 magnetic nanoparticles synthesis from tailings by ultrasonic chemical co-precipitation. Materials Letters. 2011;65:1882'},{id:"B47",body:'Pereira C et al. Superparamagnetic MFe2O4 (M = Fe, Co, Mn) nanoparticles: Tuning the particle size and magnetic properties through a novel one-step coprecipitation route. Chemistry of Materials. 2012;24:1496'},{id:"B48",body:'Li Z et al. Direct coprecipitation route to monodisperse dual functionalized magnetic iron oxide nanocrystals without size selection. Small. 2008;4:231-239'},{id:"B49",body:'Sun S, Zeng H. Size-controlled synthesis of magnetite nanoparticles. Journal of the American Chemical Society. 2002;124(28):8204-8205'},{id:"B50",body:'Hyeon T. Chemical synthesis of magnetic nanoparticles. Chemical Communications. 2003;8:927-934'},{id:"B51",body:'Xu Z et al. Organic phase synthesis of monodisperse iron oxide nanocrystals using iron chloride as precursor. Nanoscale. 2010;2(6):1027-1032'},{id:"B52",body:'Wang Y et al. One-pot reaction to synthesize superparamagnetic iron oxide nanoparticles by adding phenol as reducing agent and stabilizer. Journal of Nanoparticle Research. 2012;14:755'},{id:"B53",body:'Maity D et al. Synthesis of magnetite nanoparticles via a solvent-free thermal decomposition route. Journal of Magnetism and Magnetic Materials. 2009;321:1256-1259'},{id:"B54",body:'Asuha S et al. One step synthesis of maghemite nanoparticles by direct thermal decomposition of Fe-urea complex and their properties. Journal of Alloys and Compounds. 2009;472:L23-L25'},{id:"B55",body:'Hu M et al. Prussian blue microcrystals prepared by selective etching and their conversion to mesoporous magnetic iron(III) oxides. Chemical Communications. 2010;46(7):1133'},{id:"B56",body:'Hu M et al. Hierarchical magnetic iron (III) oxides prepared by solid-state thermal decomposition of coordination polymers. RSC Advances. 2012;2(11):4782'},{id:"B57",body:'Amara D, Margel S. Solvent less thermal decomposition of ferrocene as a new approach for the synthesis of porous superparamagnetic and ferromagnetic composite microspheres of narrow size distribution. Journal of Materials Chemistry. 2011;21(39):15764'},{id:"B58",body:'Pérez-Mirabet L et al. One-pot synthesis of stable colloidal solutions of MFe2O4 nanoparticles using oleylamine as solvent and stabilizer. Materials Research Bulletin. 2013;48(3):966-972'},{id:"B59",body:'Amara D et al. Solventless thermal decomposition of ferrocene as a new approach for one-step synthesis of magnetite nanocubes and nanospheres. Journal of Materials Chemistry. 2012;22(5):2188'},{id:"B60",body:'Lynch J et al. Gas-bubble effects on the formation of colloidal iron oxide nanocrystals. Journal of the American Chemical Society. 2011;133:12664-12674'},{id:"B61",body:'Han LH et al. In situ synthesis of hematite nanoparticles using a low-temperature microemulsion method. Powder Technology. 2011;207:42-46'},{id:"B62",body:'Wongwailikhit K, Horwongsakul S. The preparation of iron (III) oxide nanoparticles using w/o microemulsion. Materials Letters. 2011;65:2820-2822'},{id:"B63",body:'Malik MA et al. Microemulsion method: A novel route to synthesize organic and inorganic nanomaterials. 1st nano update. Arabian Journal of Chemistry. 2012;5(4):397-417'},{id:"B64",body:'Lu T et al. Surfactant effects on the microstructures of Fe3O4 nanoparticles synthesized by microemulsion method. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2013;436:675-683'},{id:"B65",body:'Ladj R et al. Individual inorganic nanoparticles: Preparation, functionalization and in vitro biomedical diagnostic applications. Journal of Materials Chemistry B. 2013;1(10):1381'},{id:"B66",body:'Tan TTY et al. Microemulsion preparative methods (overview). Comprehensive Nanoscience and Technology. 2011;5:399-441'},{id:"B67",body:'Li Y et al. Single-microemulsion-based solvothermal synthesis of magnetite microflowers. Ceramics International. 2014;40(3):4791-4795'},{id:"B68",body:'Okoli C et al. Application of magnetic iron oxide nanoparticles prepared from microemulsions for protein purification. Journal of Chemical Technology and Biotechnology. 2011;86(11):1386-1393'},{id:"B69",body:'Okoli C et al. Comparison and functionalization study of microemulsion-prepared magnetic iron oxide nanoparticles. Langmuir. 2012;28(22):8479-8485'},{id:"B70",body:'Wu W et al. Magnetic iron oxide nanoparticles: Synthesis and surface functionalization strategies. Nanoscale Research Letters. 2008;3(11):397-415'},{id:"B71",body:'Ge S et al. Facile hydrothermal synthesis of iron oxide nanoparticles with tunable magnetic properties. Journal of Physical Chemistry C. 2009;113:13593-13599'},{id:"B72",body:'Wang J et al. Synthesis of monodisperse nanocrystals of high crystallinity magnetite through solvothermal process. Materials Chemistry and Physics. 2009;113:6-9'},{id:"B73",body:'Kawai-Nakamura A et al. Rapid and continuous hydrothermal synthesis of metal and metal oxide nanoparticles with a microtube-reactor at 523 K and 30 MPa. Materials Letters. 2008;62(19):3471-3473'},{id:"B74",body:'Lin X et al. Formation mechanism and magnetic properties of hollow Fe3O4 nano-spheres synthesized without any surfactant. CrystEngComm. 2012;14(24):8658-8663'},{id:"B75",body:'Tian Y et al. Facile solvothermal synthesis of monodisperse Fe3O4 nanocrystals with precise size control of one nanometre as potential MRI contrast agents. Journal of Materials Chemistry. 2011;21(8):2476'},{id:"B76",body:'Ahmadi S et al. Synthesis of Fe3O4 nanocrystals using hydrothermal approach. Journal of Magnetism and Magnetic Materials. 2012;324(24):4147-4150'},{id:"B77",body:'Jung CH. Sintering characterization of Li2TiO3 ceramic breeder powders prepared by the solution combustion synthesis process. Journal of Nuclear Materials. 2005;341(2-3):148-152'},{id:"B78",body:'Manukyan KV et al. Solution combustion synthesis of nano-crystalline metallic materials: Mechanistic studies. Journal of Physical Chemistry C. 2013;117(46):24417-24427'},{id:"B79",body:'Jadhav LD et al. Solution combustion synthesis: Role of oxidant to fuel ratio on powder properties. Materials Sciences Forum. 2013;757:85-98'},{id:"B80",body:'Ianos R et al. Solution combustion synthesis and characterization of magnetite, Fe3O4, nanopowders. Journal of the American Ceramic Society. 2012;95(7):2236-2240'},{id:"B81",body:'Mihoc G et al. Adsorption of phenol and p-chlorophenol from aqueous solutions by magnetic nanopowder. Water Science and Technology. 2014;69(2):385-391'},{id:"B82",body:'Mihoc G et al. Combustion synthesis of some iron oxides used as adsorbents for phenol and p-chlorophenol removal from wastewater. Journal of Thermal Analysis and Calorimetry. 2013;112:391-397'},{id:"B83",body:'Ianos R et al. γ-Fe2O3 nanoparticles prepared by combustion synthesis, followed by chemical oxidation of residual carbon with H2O2. Materials Chemistry and Physics. 2014;148:705-711'},{id:"B84",body:'Rudakovskaya PG et al. Synthesis and characterization of PEG-Silane functionalized iron oxide (II, III) nanoparticles for biomedical application. Nanotechnology in Russia. 2015;10(11-12):896-903'},{id:"B85",body:'Ulbrich K et al. Targeted drug delivery with polymers and magnetic nanoparticles: Covalent and noncovalent approaches. Chemical Reviews. 2016;116:5338-5431'},{id:"B86",body:'Montazerabadi AR, et al. Development of gold-coated magnetic nanoparticles as a potential MRI contrast agent. NANO: Brief Reports and Reviews. 2015;10(4):1550048-1550059'},{id:"B87",body:'Mahmoudi M, Serpooshan V. Silver-coated engineered magnetic nanoparticles are promising for the success in the fight against antibacterial resistance threat. ACS Nano. 2012;6(3):2656-2664'},{id:"B88",body:'Yang L et al. One-pot synthesis of aldehyde-functionalized mesoporous silica-Fe3O4 nanocomposites for immobilization of penicillin G acylase. Microporous and Mesoporous Materials. 2014;197:1-7'},{id:"B89",body:'Lee HJ et al. Photothermal cancer therapy using graphitic carbon–coated magnetic particles prepared by one-pot synthesis. International Journal of Nanomedicine. 2015;10:271-282'},{id:"B90",body:'Zhang CW et al. Preparation and characterization of surface-functionalization of silica-coated magnetite nanoparticles for drug delivery. NANO: Brief Reports and Reviews. 2014;9(4):1450042-1450050'},{id:"B91",body:'Yarjanli Z et al. Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation. BMC Neuroscience. 2017;18(1):51. DOI: 10.1186/s12868-017-0369-9'},{id:"B92",body:'Farshbaf MJ, Ghaedi K. Does any drug to treat cancer target mTOR and iron hemostasis in neurodegenerative disorders? Biometals. 2017;30(1):1-16. DOI: 10.1007/s10534-016-9981-x'},{id:"B93",body:'Pinkernelle J et al. Magnetic nanoparticles in primary neural cell cultures are mainly taken up by microglia. BMC Neuroscience. 2012;13:32. DOI: 10.1186/1471-2202-13-32'},{id:"B94",body:'Mazuel F et al. Massive intracellular biodegradation of iron oxide nanoparticles evidenced magnetically at single-endosome and tissue levels. ACS Nano. 2016;10:7627-7638'},{id:"B95",body:'Pongrac IM et al. Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles. International Journal of Nanomedicine. 2016;11:1701-1715'},{id:"B96",body:'Calero M et al. Efficient and safe internalization of magnetic iron oxide nanoparticles: Two fundamental requirements for biomedical applications. Nanomedicine: Nanotechnology, Biology, and Medicine. 2014;10:733-743. DOI: 10.1016/j.nano.2013.11.010'},{id:"B97",body:'Wu W et al. Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications. Science and Technology of Advanced Materials. 2015;16:023501 (43 p). DOI: 10.1088/1468-6996/16/2/023501'},{id:"B98",body:'Li L et al. Comparative In Vitro cytotoxicity study on uncoated magnetic nanoparticles: Effects on cell viability, cell morphology, and cellular uptake. Journal for Nanoscience and Nanotechnology. 2012;12:1-8. DOI: 10.1166/jnn.2012.6755'},{id:"B99",body:'Cortajarena AL et al. Engineering iron oxide nanoparticles for clinical settings. Nano. 2014;1(2):1-20'},{id:"B100",body:'Coricovac DE et al. Biocompatible colloidal suspensions based on magnetic iron oxide nanoparticles: Synthesis, characterization and toxicological profile. Frontiers in Pharmacology. 2017;8:154. DOI: 10.3389/fphar.2017.00154'},{id:"B101",body:'Shelat R et al. Detailed toxicity evaluation of β-cyclodextrin coated iron oxide nanoparticles for biomedical applications. International Journal of Biological Macromolecules. 2018;110:357-365. DOI: 10.1016/j.ijbiomac.2017.09.067'},{id:"B102",body:'Bostan HB et al. Cardiotoxicity of nano-particles. Life Sciences. 2016;165:91-99. DOI: 10.1016/j.lfs.2016.09.017'},{id:"B103",body:'Dissanayake NM et al. Mutagenic effects of iron oxide nanoparticles on biological cells. International Journal of Molecular Sciences. 2015;16(10):23482-23516. DOI: 10.3390/ijms161023482'},{id:"B104",body:'Montiel Schneider MG, Lassalle VL. Magnetic iron oxide nanoparticles as novel and efficient tools for atherosclerosis diagnosis. Biomedicine & Pharmacotherapy. 2017;93:1098-1115. DOI: 10.1016/j.biopha.2017.07.012'},{id:"B105",body:'Mohammed L, et al. Magnetic nanoparticles for environmental and biomedical applications: A review. Particuology. 2017;30:1-14. DOI: 10.1016/j.partic.2016.06.001'},{id:"B106",body:'Paunescu V et al. Enucleation: A possible mechanism of cancer cell death. Journal of Cellular and Molecular Medicine. 2014;18(6):962-965. DOI: 10.1111/jcmm.12271'},{id:"B107",body:'Singhal M et al. Enucleation sign: A computed tomographic appearance of ruptured hepatocellular carcinoma. Journal of Clinical and Experimental Hepatology. 2016;6(4):335-336. DOI: 10.1016/j.jceh.2016.05.004'},{id:"B108",body:'Zavisova V et al. The cytotoxicity of iron oxide nanoparticles with different modifications evaluated in vitro. Journal of Magnetism and Magnetic Materials. 2015;380:85-89'},{id:"B109",body:'Available from: https://clinicaltrials.gov/ct2/show/NCT01169935?term=Endorem&rank=9'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Elena-Alina Moacă",address:null,affiliation:'
Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Romania
Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Romania
'}],corrections:null},book:{id:"6335",title:"Iron Ores and Iron Oxide Materials",subtitle:null,fullTitle:"Iron Ores and Iron Oxide Materials",slug:"iron-ores-and-iron-oxide-materials",publishedDate:"July 11th 2018",bookSignature:"Volodymyr Shatokha",coverURL:"https://cdn.intechopen.com/books/images_new/6335.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"111000",title:"Dr.",name:"Volodymyr",middleName:null,surname:"Shatokha",slug:"volodymyr-shatokha",fullName:"Volodymyr Shatokha"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"61492",title:"The Chinese Iron Ore Deposits and Ore Production",slug:"the-chinese-iron-ore-deposits-and-ore-production",totalDownloads:972,totalCrossrefCites:1,signatures:"Guangrong Li",authors:[{id:"216668",title:"Prof.",name:"Guangrong",middleName:null,surname:"Li",fullName:"Guangrong Li",slug:"guangrong-li"}]},{id:"60959",title:"Genesis, Uses and Environment Implications of Iron Oxides and Ores",slug:"genesis-uses-and-environment-implications-of-iron-oxides-and-ores",totalDownloads:860,totalCrossrefCites:0,signatures:"Davidson E. Egirani, Mohd T. Latif, Nanfe R. Poyi, Napoleon Wessey\nand Shukla Acharjee",authors:[{id:"217113",title:"Dr.",name:"Davidson",middleName:null,surname:"Egirani",fullName:"Davidson Egirani",slug:"davidson-egirani"},{id:"227028",title:"Dr.",name:"Shukla",middleName:null,surname:"Acharjee",fullName:"Shukla Acharjee",slug:"shukla-acharjee"},{id:"229260",title:"Prof.",name:"Mohamed",middleName:null,surname:"Latif",fullName:"Mohamed Latif",slug:"mohamed-latif"},{id:"229261",title:"Ms.",name:"Nanfe",middleName:null,surname:"Poyi",fullName:"Nanfe Poyi",slug:"nanfe-poyi"},{id:"229262",title:"Dr.",name:"Napoleon",middleName:null,surname:"Wessey",fullName:"Napoleon Wessey",slug:"napoleon-wessey"}]},{id:"58868",title:"Iron Ore Pelletizing Process: An Overview",slug:"iron-ore-pelletizing-process-an-overview",totalDownloads:3198,totalCrossrefCites:2,signatures:"Sandra Lúcia de Moraes, José Renato Baptista de Lima and Tiago\nRamos Ribeiro",authors:[{id:"216788",title:"Dr.",name:"Sandra",middleName:"Lúcia",surname:"De Moraes",fullName:"Sandra De Moraes",slug:"sandra-de-moraes"},{id:"233466",title:"Prof.",name:"José Renato Baptista",middleName:null,surname:"De Lima",fullName:"José Renato Baptista De Lima",slug:"jose-renato-baptista-de-lima"},{id:"233467",title:"MSc.",name:"Tiago Ramos",middleName:null,surname:"Ribeiro",fullName:"Tiago Ramos Ribeiro",slug:"tiago-ramos-ribeiro"}]},{id:"58288",title:"Iron Ore Agglomeration Technologies",slug:"iron-ore-agglomeration-technologies",totalDownloads:932,totalCrossrefCites:7,signatures:"Daniel Fernández-González, Juan Piñuela-Noval and Luis Felipe\nVerdeja",authors:[{id:"211395",title:"MSc.",name:"Daniel",middleName:null,surname:"Fernández González",fullName:"Daniel Fernández González",slug:"daniel-fernandez-gonzalez"},{id:"212958",title:"Dr.",name:"Luis Felipe",middleName:null,surname:"Verdeja González",fullName:"Luis Felipe Verdeja González",slug:"luis-felipe-verdeja-gonzalez"},{id:"229106",title:"Mr.",name:"Juan",middleName:null,surname:"Piñuela-Noval",fullName:"Juan Piñuela-Noval",slug:"juan-pinuela-noval"}]},{id:"58482",title:"Calcination and Pelletizing of Siderite Ore",slug:"calcination-and-pelletizing-of-siderite-ore",totalDownloads:633,totalCrossrefCites:0,signatures:"Mehmet Celikdemir, Musa Sarikaya, Tolga Depci, Ramazan\nAydogmus and Aysegul Yucel",authors:[{id:"212301",title:"M.Sc.",name:"Mehmet",middleName:null,surname:"Çelikdemir",fullName:"Mehmet Çelikdemir",slug:"mehmet-celikdemir"},{id:"213405",title:"Prof.",name:"Musa",middleName:null,surname:"Sarikaya",fullName:"Musa Sarikaya",slug:"musa-sarikaya"},{id:"213412",title:"Prof.",name:"Tolga",middleName:null,surname:"Depci",fullName:"Tolga Depci",slug:"tolga-depci"},{id:"213413",title:"MSc.",name:"Ramazan",middleName:null,surname:"Aydoğmuş",fullName:"Ramazan Aydoğmuş",slug:"ramazan-aydogmus"},{id:"227119",title:"MSc.",name:"Ayşegül",middleName:null,surname:"Yücel",fullName:"Ayşegül Yücel",slug:"aysegul-yucel"}]},{id:"55044",title:"Mechanism and Prevention of Agglomeration/Defluidization during Fluidized-Bed Reduction of Iron Ore",slug:"mechanism-and-prevention-of-agglomeration-defluidization-during-fluidized-bed-reduction-of-iron-ore",totalDownloads:495,totalCrossrefCites:0,signatures:"Yiwei Zhong, Jintao Gao, Zhancheng Guo and Zhi Wang",authors:[{id:"195676",title:"Dr.",name:"Yiwei",middleName:null,surname:"Zhong",fullName:"Yiwei Zhong",slug:"yiwei-zhong"},{id:"196894",title:"Dr.",name:"Jintao",middleName:null,surname:"Gao",fullName:"Jintao Gao",slug:"jintao-gao"},{id:"196895",title:"Prof.",name:"Zhancheng",middleName:null,surname:"Guo",fullName:"Zhancheng Guo",slug:"zhancheng-guo"},{id:"196913",title:"Prof.",name:"Zhi",middleName:null,surname:"Wang",fullName:"Zhi Wang",slug:"zhi-wang"}]},{id:"60279",title:"The eXtended Discrete Element Method (XDEM): An Advanced Approach to Model Blast Furnace",slug:"the-extended-discrete-element-method-xdem-an-advanced-approach-to-model-blast-furnace",totalDownloads:526,totalCrossrefCites:0,signatures:"Bernhard Peters, Maryam Baniasadi and Mehdi Baniasadi",authors:[{id:"226356",title:"Prof.",name:"Bernhard",middleName:null,surname:"Peters",fullName:"Bernhard Peters",slug:"bernhard-peters"},{id:"226358",title:"MSc.",name:"Maryam",middleName:null,surname:"Baniasadi",fullName:"Maryam Baniasadi",slug:"maryam-baniasadi"},{id:"226361",title:"MSc.",name:"Mehdi",middleName:null,surname:"Baniasadi",fullName:"Mehdi Baniasadi",slug:"mehdi-baniasadi"}]},{id:"59113",title:"Photoelectrochemistry of Hematite",slug:"photoelectrochemistry-of-hematite",totalDownloads:486,totalCrossrefCites:0,signatures:"Yasuhisa Maeda",authors:[{id:"213447",title:"Prof.",name:"Yasuhisa",middleName:null,surname:"Maeda",fullName:"Yasuhisa Maeda",slug:"yasuhisa-maeda"}]},{id:"58309",title:"Iron Oxide-Based Catalyst for Catalytic Cracking of Heavy Oil",slug:"iron-oxide-based-catalyst-for-catalytic-cracking-of-heavy-oil",totalDownloads:609,totalCrossrefCites:0,signatures:"Eri Fumoto, Shinya Sato and Toshimasa Takanohashi",authors:[{id:"36763",title:"Dr.",name:"Eri",middleName:null,surname:"Fumoto",fullName:"Eri Fumoto",slug:"eri-fumoto"},{id:"229413",title:"Dr.",name:"Shinya",middleName:null,surname:"Sato",fullName:"Shinya Sato",slug:"shinya-sato"},{id:"229414",title:"Dr.",name:"Toshimasa",middleName:null,surname:"Takanohashi",fullName:"Toshimasa Takanohashi",slug:"toshimasa-takanohashi"}]},{id:"58152",title:"Mn-Zn Ferrite as Recycled Material Resource Based on Iron Oxide Suitable to Functional Green Devices",slug:"mn-zn-ferrite-as-recycled-material-resource-based-on-iron-oxide-suitable-to-functional-green-devices",totalDownloads:588,totalCrossrefCites:0,signatures:"Roberto Baca",authors:[{id:"199138",title:"Dr.",name:"Roberto",middleName:null,surname:"Baca",fullName:"Roberto Baca",slug:"roberto-baca"}]},{id:"60610",title:"The Investigation of Removing Direct Blue 15 Dye from Wastewater Using Magnetic Luffa sponge NPs",slug:"the-investigation-of-removing-direct-blue-15-dye-from-wastewater-using-magnetic-luffa-sponge-nps",totalDownloads:634,totalCrossrefCites:0,signatures:"Hayrunnisa Nadaroglu, Semra Cicek, Hicran Onem and Azize Alayli\nGungor",authors:[{id:"221608",title:"Prof.",name:"Hayrunnisa",middleName:null,surname:"Nadaroglu",fullName:"Hayrunnisa Nadaroglu",slug:"hayrunnisa-nadaroglu"},{id:"226435",title:"Prof.",name:"Azize",middleName:null,surname:"Alayli Gungor",fullName:"Azize Alayli Gungor",slug:"azize-alayli-gungor"},{id:"226436",title:"Dr.",name:"Semra",middleName:null,surname:"Cicek",fullName:"Semra Cicek",slug:"semra-cicek"}]},{id:"60330",title:"Preclinical Aspects on Magnetic Iron Oxide Nanoparticles and Their Interventions as Anticancer Agents: Enucleation, Apoptosis and Other Mechanism",slug:"preclinical-aspects-on-magnetic-iron-oxide-nanoparticles-and-their-interventions-as-anticancer-agent",totalDownloads:730,totalCrossrefCites:5,signatures:"Elena-Alina Moacă, Elena Dorina Coricovac, Codruta Marinela\nSoica, Iulia Andreea Pinzaru, Cornelia Silvia Păcurariu and Cristina\nAdriana Dehelean",authors:[{id:"141027",title:"Dr.",name:"Cristina",middleName:null,surname:"Dehelean",fullName:"Cristina Dehelean",slug:"cristina-dehelean"},{id:"173283",title:"Dr.",name:"Dorina",middleName:null,surname:"Coricovac",fullName:"Dorina Coricovac",slug:"dorina-coricovac"},{id:"186678",title:"Dr.",name:"Codruta",middleName:null,surname:"Soica",fullName:"Codruta Soica",slug:"codruta-soica"},{id:"217849",title:"Associate Prof.",name:"Iulia Andreea",middleName:null,surname:"Pinzaru",fullName:"Iulia Andreea Pinzaru",slug:"iulia-andreea-pinzaru"},{id:"219727",title:"Mrs.",name:"Elena Alina",middleName:null,surname:"Moaca",fullName:"Elena Alina Moaca",slug:"elena-alina-moaca"},{id:"219728",title:"Prof.",name:"Cornelia Silvia",middleName:null,surname:"Pacurariu",fullName:"Cornelia Silvia Pacurariu",slug:"cornelia-silvia-pacurariu"}]},{id:"59047",title:"Bandgap-Engineered Iron Oxides for Solar Energy Harvesting",slug:"bandgap-engineered-iron-oxides-for-solar-energy-harvesting",totalDownloads:613,totalCrossrefCites:1,signatures:"Munetoshi Seki",authors:[{id:"218267",title:"Associate Prof.",name:"Munetoshi",middleName:null,surname:"Seki",fullName:"Munetoshi Seki",slug:"munetoshi-seki"}]}]},relatedBooks:[{type:"book",id:"2132",title:"Sintering",subtitle:"Methods and Products",isOpenForSubmission:!1,hash:"a4374d54a1172051ff65e9f3aebee8f3",slug:"sintering-methods-and-products",bookSignature:"Volodymyr Shatokha",coverURL:"https://cdn.intechopen.com/books/images_new/2132.jpg",editedByType:"Edited by",editors:[{id:"111000",title:"Dr.",name:"Volodymyr",surname:"Shatokha",slug:"volodymyr-shatokha",fullName:"Volodymyr Shatokha"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"33160",title:"Latest Generation Sinter Process Optimization Systems",slug:"latest-generation-sinter-process-optimization-systems",signatures:"Thomas Kronberger, Martin Schaler and Christoph Schönegger",authors:[{id:"12019",title:"Dr.",name:"Thomas",middleName:null,surname:"Kronberger",fullName:"Thomas Kronberger",slug:"thomas-kronberger"}]},{id:"33161",title:"Modeling Sintering Process of Iron Ore",slug:"modeling-sintering-process-of-iron-ore",signatures:"Jose Adilson de Castro",authors:[{id:"96342",title:"Dr",name:null,middleName:null,surname:"De Castro",fullName:"De Castro",slug:"de-castro"}]},{id:"33162",title:"Development of Sintered MCrAlY Alloys for Aeronautical Applications",slug:"development-of-mcral-y-alloys-sintered-for-aeronautical-applications",signatures:"Fernando Juárez López and Ricardo Cuenca Alvarez",authors:[{id:"92443",title:"Dr.",name:"Fernando",middleName:null,surname:"Juarez Lopez",fullName:"Fernando Juarez Lopez",slug:"fernando-juarez-lopez"},{id:"136071",title:"Dr.",name:"Ricardo",middleName:null,surname:"Cuenca-Alvarez",fullName:"Ricardo Cuenca-Alvarez",slug:"ricardo-cuenca-alvarez"}]},{id:"33163",title:"Metal Laser Sintering for Rapid Tooling in Application to Tyre Tread Pattern Mould",slug:"metal-laser-sintering-for-rapid-tooling-in-application-to-tyre-tread-pattern-mould-",signatures:"Jelena Milovanovic, Milos Stojkovic and Miroslav Trajanovic",authors:[{id:"103700",title:"MSc.",name:"Jelena",middleName:null,surname:"Milovanovic",fullName:"Jelena Milovanovic",slug:"jelena-milovanovic"},{id:"106627",title:"Dr.",name:"Milos",middleName:null,surname:"Stojkovic",fullName:"Milos Stojkovic",slug:"milos-stojkovic"},{id:"106628",title:"Prof.",name:"Miroslav",middleName:null,surname:"Trajanovic",fullName:"Miroslav Trajanovic",slug:"miroslav-trajanovic"}]},{id:"33164",title:"Sintering of Supported Metal Catalysts",slug:"sintering-of-supported-metal-catalysts-",signatures:"José Luis Contreras and Gustavo A. Fuentes",authors:[{id:"94936",title:"Dr.",name:"José Luis",middleName:null,surname:"Contreras",fullName:"José Luis Contreras",slug:"jose-luis-contreras"}]},{id:"33165",title:"Sintering Characteristics of Injection Moulded 316L Component Using Palm-Based Biopolymer Binder",slug:"sintering-characteristics-of-injection-moulded-components-using-palm-based-biopolymer-binder-",signatures:"Mohd Afian Omar and Istikamah Subuki",authors:[{id:"92498",title:"Dr.",name:"Mohd Afian",middleName:null,surname:"Omar",fullName:"Mohd Afian Omar",slug:"mohd-afian-omar"},{id:"121113",title:"Dr.",name:"Istiqamah",middleName:null,surname:"Subuki",fullName:"Istiqamah Subuki",slug:"istiqamah-subuki"}]},{id:"33166",title:"Liquid Phase Sintering of Fe-Cu-Sn-Pb System for Tribological Applications",slug:"liquid-phase-sintering-of-fe-cu-sn-pb-system-for-tribological-applications",signatures:"Cristina Teisanu",authors:[{id:"92226",title:"Dr.",name:"Cristina",middleName:null,surname:"Teisanu",fullName:"Cristina Teisanu",slug:"cristina-teisanu"}]},{id:"33167",title:"Photonic Sintering of Silver Nanoparticles: Comparison of Experiment and Theory",slug:"photonic-sintering-of-silver-nanoparticles-comparison-of-experiment-and-theory",signatures:"Jeff West, Michael Carter, Steve Smith and James Sears",authors:[{id:"95958",title:"Dr.",name:"Jeff",middleName:null,surname:"West",fullName:"Jeff West",slug:"jeff-west"},{id:"100438",title:"MSc.",name:"Michael",middleName:null,surname:"Carter",fullName:"Michael Carter",slug:"michael-carter"},{id:"100439",title:"Dr.",name:"Steve",middleName:null,surname:"Smith",fullName:"Steve Smith",slug:"steve-smith"},{id:"100441",title:"Dr.",name:"James",middleName:null,surname:"Sears",fullName:"James Sears",slug:"james-sears"}]},{id:"33168",title:"Microwave-Induced Combustion Synthesis of Luminescent Aluminate Powders",slug:"microwave-induced-combustion-synthesis-of-luminescent-aluminate-powders",signatures:"A. Potdevin, N. Pradal, M.-L. François, G. Chadeyron, D. Boyer and R. Mahiou",authors:[{id:"99443",title:"Dr.",name:"Damien",middleName:null,surname:"Boyer",fullName:"Damien Boyer",slug:"damien-boyer"},{id:"133418",title:"Dr.",name:"Audrey",middleName:null,surname:"Potdevin",fullName:"Audrey Potdevin",slug:"audrey-potdevin"},{id:"133419",title:"Ms.",name:"Nathalie",middleName:null,surname:"Pradal",fullName:"Nathalie Pradal",slug:"nathalie-pradal"},{id:"133420",title:"Prof.",name:"Geneviève",middleName:null,surname:"Chadeyron",fullName:"Geneviève Chadeyron",slug:"genevieve-chadeyron"},{id:"133421",title:"Dr.",name:"Rachid",middleName:null,surname:"Mahiou",fullName:"Rachid Mahiou",slug:"rachid-mahiou"}]},{id:"33184",title:"On the Application of 3D X-Ray Microtomography for Studies in the Field of Iron Ore Sintering Technology",slug:"on-the-application-of-3d-x-ray-microtomography-for-studies-in-the-field-of-iron-ore-sintering-techno",signatures:"Volodymyr Shatokha, Iurii Korobeynikov and Eric Maire",authors:[{id:"111000",title:"Dr.",name:"Volodymyr",middleName:null,surname:"Shatokha",fullName:"Volodymyr Shatokha",slug:"volodymyr-shatokha"},{id:"129851",title:"Mr.",name:"Iurii",middleName:null,surname:"Korobeynikov",fullName:"Iurii Korobeynikov",slug:"iurii-korobeynikov"},{id:"129854",title:"Dr.",name:"Eric",middleName:null,surname:"Maire",fullName:"Eric Maire",slug:"eric-maire"}]},{id:"33185",title:"Effect of the Additives of Nanosized Nb and Ta Carbides on Microstructure and Properties of Sintered Stainless Steel",slug:"-effect-of-the-additives-of-nanosized-nb-and-ta-carbides-on-microstructure-and-properties-of-sintere",signatures:"Uílame Umbelino Gomes, José Ferreira da Silva Jr. and Gislâine Bezerra Pinto Ferreira",authors:[{id:"98760",title:"MSc.",name:"Gislaine",middleName:"Bezerra Pinto",surname:"Ferreira",fullName:"Gislaine Ferreira",slug:"gislaine-ferreira"},{id:"102381",title:"Dr.",name:"Uílame Umbelino",middleName:null,surname:"Gomes",fullName:"Uílame Umbelino Gomes",slug:"uilame-umbelino-gomes"},{id:"133481",title:"Prof.",name:"Jose Ferreira",middleName:null,surname:"Silva Jr",fullName:"Jose Ferreira Silva Jr",slug:"jose-ferreira-silva-jr"}]},{id:"33186",title:"Properties and Structure of Sintered Boron Containing Carbon Steels",slug:"properties-and-structure-of-sintered-boron-containing-carbon-steels-",signatures:"G. Bagliuk",authors:[{id:"99424",title:"Dr.",name:"Gennadii",middleName:null,surname:"BaglIuk",fullName:"Gennadii BaglIuk",slug:"gennadii-bagliuk"}]},{id:"33187",title:"Influence of Sintering Temperature on Magnetotransport Behavior of Some Nanocrystalline Manganites",slug:"influence-of-sintering-temperature-on-magnetotransport-behavior-of-some-nanocrystalline-manganites",signatures:"G. Venkataiah , Y. Kalyana Lakshmi and P. Venugopal Reddy",authors:[{id:"98705",title:"Prof.",name:"Paduru",middleName:null,surname:"Venugopal Reddy",fullName:"Paduru Venugopal Reddy",slug:"paduru-venugopal-reddy"},{id:"165472",title:"Dr.",name:"Venkataiah",middleName:null,surname:"Gorige",fullName:"Venkataiah Gorige",slug:"venkataiah-gorige"}]},{id:"33188",title:"The Quantification of Crystalline Phases in Materials: Applications of Rietveld Method",slug:"the-quantification-of-crystalline-phases-in-materials-applications-of-rietveld-method",signatures:"Cláudia T. Kniess, João Cardoso de Lima and Patrícia B. Prates",authors:[{id:"99987",title:"Dr.",name:"Cláudia",middleName:null,surname:"Kniess",fullName:"Cláudia Kniess",slug:"claudia-kniess"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"64120",title:"Introductory Chapter: Gas Chromatography - The Most Versatile Analytical Technique",doi:"10.5772/intechopen.81693",slug:"introductory-chapter-gas-chromatography-the-most-versatile-analytical-technique",body:'\n
\n
1. Definition and short history of gas chromatography
\n
Gas chromatography (GC) is a type of chromatography. According to the International Union of Pure and Applied Chemistry (IUPAC) recommendation, gas chromatography is defined as a separation technique in which the mobile phase is a gas. Gas chromatography is always carried out in a column [1]. GC is a separation and detection method for sample mixtures, whose components can be volatilized without thermal decomposition. The analytical procedure is used for the determination of organic substances; usually molecules have a molecular mass of less than 500 g/mol and a boiling point of less than 400°C. GC is a technique used to separate mixtures of gaseous chemical compounds based on differences in the compounds’ relative affinities for a solid (gas-solid chromatography) or liquid (gas-liquid chromatography) stationary phase held within a column.
\n
Gas-liquid partition chromatography was invented by Martin and James from the National Institute for Medical Research, London, in 1952. The invention of this technique is generally attributed to the inventors in their 1952 published paper in the Biochemical Journal [2]. In this publication the theory of the partition column has been extended to cover a compressible mobile phase, and gas-liquid partition columns were described for the separation of volatile fatty acids. In the same year, the Nobel Prize in chemistry was awarded jointly to Martin and Synge for their invention of partition chromatography. Starting from this time, gas chromatography has become one of the most important and widely applied analytical techniques in modern chemistry. The first commercial gas chromatograph was introduced in 1955 by Perkin-Elmer (USA). Subsequently, this method was used to study petrochemical products. Today, gas chromatography is one of the most widespread investigation methods of instrumental analysis. This technique is used in the laboratories of the chemical, petrochemical, and pharmaceutical industries, in the research institutes and also in the clinical and environmental and food and beverage analyses. Recent developments in GC have resulted in the introduction of better and selective fused silica capillary columns and methods for sample preparation. Newer separation and detection solutions, such as fast GC, multidimensional separation GC techniques (GC × GC), and hyphenation of GC and GC × GC with mass spectrometry (MS), with triple quadrupole mass spectrometry and with time-of-flight mass spectrometry (TOF-MS), have been developed and become industrial routine. Analytical pyrolysis (Py) technique hyphenated to GC and GC/MS has extended the range of possible tools for the characterization of synthetic polymers and copolymers. This technique has been used extensively over the last 30 years as a complementary analytical tool used to characterize the structure of synthetic organic polymers and copolymers, polymer blends, biopolymers, and natural resins [3].
\n
\n
\n
2. Multidimensional gas chromatography
\n
Developed by Phillips and coworker at the Southern Illinois University (USA) in the early 1990s, comprehensive multidimensional GC (GC × GC or 2D GC) is a powerful technique for samples containing very large numbers of compounds of interest and also for samples which exhibit high chemical complexity. This technique can be used to separate very complex mixtures, such as those found in the petrochemical, environmental, and food and fragrance industries [4, 5, 6]. The method uses two capillary columns, typically of very different polarities, installed in series with a modulator in between. The first column is in principle nonpolar or low polar, and the second column is polar. The length of the first column might typically be 20–30 m, the inner diameter 0.25 mm, and the film thickness 0.25 μm. The second column is typically shorter (1–2 m), the inner diameter is narrower (0.1 mm), and the stationary phase is thinner (0.1 μm), to allow for faster separations. The entire assembly is located inside the GC oven [6]. The modulator collects effluent from the first column for a fraction of the time equal to peak width. The modulator focuses the material collected from each cut into a very narrow band through flow compression. It introduces the bands sequentially onto the second column, resulting in additional separation for each band injected onto the second column [4, 5, 6, 7, 8, 9]. The most common data transformation is the construction of a 2D representation, in which one axis represents the separation on the first column (first dimension), and the other axis represents the secondary column separation (second dimension). Therefore, the look of GC × GC chromatograms appears completely different from conventional GC chromatogram showing a two-dimensional plane where analyte spots are scattered about [7, 8]. A contour plot, using elevation lines or color coding, represents the signal intensity. 2D GC data are primarily used for qualitative analysis; however, quantitative multidimensional GC analysis is also possible [9]. Figure 1 shows an exemplary 2D GC plot of a refinery stream boiling at diesel temperature range [10].
\n
Figure 1.
2D GC plot of a refinery stream boiling at diesel temperature range. The scale indicates the relative signal intensity. Figure reprinted from Ref. [10] with permission from ACS.
\n
In this book, state of the art of gas chromatography and new developments and applications are presented. New sample preparation techniques, derivatization methods, and hyphenation with mass spectrometry are described.
\n
\n\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/64120.pdf",chapterXML:"https://mts.intechopen.com/source/xml/64120.xml",downloadPdfUrl:"/chapter/pdf-download/64120",previewPdfUrl:"/chapter/pdf-preview/64120",totalDownloads:766,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 12th 2018",dateReviewed:"September 26th 2018",datePrePublished:"November 5th 2018",datePublished:"September 4th 2019",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/64120",risUrl:"/chapter/ris/64120",signatures:"Peter Kusch",book:{id:"6831",title:"Gas Chromatography",subtitle:"Derivatization, Sample Preparation, Application",fullTitle:"Gas Chromatography - Derivatization, Sample Preparation, Application",slug:"gas-chromatography-derivatization-sample-preparation-application",publishedDate:"September 4th 2019",bookSignature:"Peter Kusch",coverURL:"https://cdn.intechopen.com/books/images_new/6831.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"254714",title:"Dr.",name:"Peter",middleName:null,surname:"Kusch",slug:"peter-kusch",fullName:"Peter Kusch"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"254714",title:"Dr.",name:"Peter",middleName:null,surname:"Kusch",fullName:"Peter Kusch",slug:"peter-kusch",email:"ptrkusch@arcor.de",position:null,institution:{name:"Bonn-Rhein-Sieg University of Applied Sciences",institutionURL:null,country:{name:"Germany"}}}],sections:[{id:"sec_1",title:"1. Definition and short history of gas chromatography",level:"1"},{id:"sec_2",title:"2. Multidimensional gas chromatography",level:"1"}],chapterReferences:[{id:"B1",body:'IUPAC Compendium of Chemical Terminology, International Union of Pure and Applied Chemistry, Version 2.3.3. 2014\n'},{id:"B2",body:'James AT, Martin AJP. Gas-liquid partition chromatography: The separation and micro-estimation of volatile fatty acids from formic acid to dodecanoic acid. The Biochemical Journal. 1952;50(5):679-690\n'},{id:"B3",body:'Kusch P. Pyrolysis—Gas Chromatography/Mass Spectrometry of Polymeric Materials. London, UK: World Scientific Europe; 2018\n'},{id:"B4",body:'Liu Z, Phillips JB. Comprehensive two-dimensional gas chromatography using an on column thermal modulator interface. Journal of Chromatographic Science. 1991;29(6):227-231\n'},{id:"B5",body:'Phillips JB, Xu J. Comprehensive multi-dimensional gas chromatography. Journal of Chromatography A. 1995;703:327-334\n'},{id:"B6",body:'Comprehensive GC System Based on Flow Modulation for the 7890A GC, Application Brief. Wilmington, DE, USA: Agilent Technologies; 2008\n'},{id:"B7",body:'Hinshaw JV. Comprehensive two-dimensional gas chromatography. LCGC Europe. 2004;17(2):86-95\n'},{id:"B8",body:'Mondello L. GC × GC Handbook, Fundamental Principles of Comprehensive 2D GC. Japan: Shimadzu; 2012\n'},{id:"B9",body:'Taylor T. A short introduction to multidimensional GC. LCGC North America. 2012;30(9):870\n'},{id:"B10",body:'Wang FC, Qiang K, Green LA. GCxMS of diesel: A two-dimensional separation approach. Analytical Chemistry. 2005;77(9):2777-2785\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Peter Kusch",address:"ptrkusch@arcor.de",affiliation:'
Department of Applied Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, Rheinbach, Germany
'}],corrections:null},book:{id:"6831",title:"Gas Chromatography",subtitle:"Derivatization, Sample Preparation, Application",fullTitle:"Gas Chromatography - Derivatization, Sample Preparation, Application",slug:"gas-chromatography-derivatization-sample-preparation-application",publishedDate:"September 4th 2019",bookSignature:"Peter Kusch",coverURL:"https://cdn.intechopen.com/books/images_new/6831.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"254714",title:"Dr.",name:"Peter",middleName:null,surname:"Kusch",slug:"peter-kusch",fullName:"Peter Kusch"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"111543",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Kawanabe",email:"kawanabe@energy.kyoto-u.ac.jp",fullName:"Hiroshi Kawanabe",slug:"hiroshi-kawanabe",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Kyoto University",institutionURL:null,country:{name:"Japan"}}},booksEdited:[],chaptersAuthored:[{title:"Ignition Process in a Non-Homogeneous Mixture",slug:"ignition-process-in-a-non-homogeneous-mixture",abstract:null,signatures:"Hiroshi Kawanabe",authors:[{id:"111543",title:"Dr.",name:"Hiroshi",surname:"Kawanabe",fullName:"Hiroshi Kawanabe",slug:"hiroshi-kawanabe",email:"kawanabe@energy.kyoto-u.ac.jp"}],book:{title:"Chemical Kinetics",slug:"chemical-kinetics",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"41971",title:"Prof.",name:"Elena",surname:"Kustova",slug:"elena-kustova",fullName:"Elena Kustova",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"52758",title:"Prof.",name:"Ekaterina",surname:"Nagnibeda",slug:"ekaterina-nagnibeda",fullName:"Ekaterina Nagnibeda",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"111189",title:"Dr.",name:"Stefano",surname:"Zambelli",slug:"stefano-zambelli",fullName:"Stefano Zambelli",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dr. Scholl Foundation",institutionURL:null,country:{name:"United States of America"}}},{id:"111613",title:"Prof.",name:"Terese",surname:"Løvås",slug:"terese-lovas",fullName:"Terese Løvås",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Norwegian University of Science and Technology",institutionURL:null,country:{name:"Norway"}}},{id:"111622",title:"Prof.",name:"Ocktaeck",surname:"Lim",slug:"ocktaeck-lim",fullName:"Ocktaeck Lim",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ulsan",institutionURL:null,country:{name:"Korea, South"}}},{id:"112457",title:"Prof.",name:"Victor",surname:"Martinez-Luaces",slug:"victor-martinez-luaces",fullName:"Victor Martinez-Luaces",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/112457/images/2263_n.png",biography:"Prof. Victor MARTINEZ-LUACES\r\nProf. Victor Martinez-Luaces has three degrees from the State University of Uruguay (UdelaR),\r\nhis first in Chemistry (Faculty of Chemistry), the second in Chemical Engineering (Faculty of Engineering) and the third in Mathematics (Faculty of Sciences). Later, he obtained a Master Degree in Didactics of Mathematics at the University of Granada (UGR, Spain).\r\nFor 25 years he has worked in four separate faculties within UdelaR (Chemistry, Economics,\r\nEngineering and Sciences), and held the position of the head of the Mathematics Department in\r\nthe Chemistry Faculty between 1996 and 2002.\r\nDuring 2006 and 2007, he moved to Rio Gallegos, Argentina, where he worked at the CIEP\r\n(Education & Research Institute) coming back to Uruguay in 2008. Since 2009 he is working as\r\nmathematical and engineering consultant at the Julio Ricaldoni Fundation, involved in research and\r\nindustrial projects of the Faculty of Engineering, at UdelaR.\r\nHe published his first book chapter in 1982 in Uruguay and first research paper in 1988, in the\r\nJournal of Chemical Education, in U.S.A. Since then, his papers have been published worldwide in\r\nthe fields of Mathematics, Chemistry, Engineering and Education in journals, proceedings and\r\nbooks.\r\nHe has seven book chapters published in U.S.A., five books in Europe and others in Singapore and Uruguay.\r\nHe been awarded several prizes:\r\n• Journal of Chemical Education – (Ethyl Corporation, 1988).\r\n• Best teacher award (Faculty of Engineering, 1992).\r\n• Best teacher award (Faculty of Engineering, 1996).\r\n• 2nd prize RELME 13 (Santo Domingo, Dominican Republic, 1999)\r\n• 2nd prize RELME 14 (Panama, 2000)\r\n• 2nd prize RELME 15 (Buenos Aires, Argentina, 2001)\r\n• 1st prize RELME 16 (La Habana, Cuba, 2002)\r\n• 1st prize RELME 19 (Montevideo, Uruguay, 2005)\r\n• Distinguished visitor of the first city in the Americas (Santo Domingo, 1999)\r\nHe has worked as a consultant for the following companies: Gautier, Roemmers, Haymann, Bader, Zenda,\r\nSkaphia and Uruguayan state institutions: OSE (Water Supply Systems), UTE (Electricity\r\nTransmission and Distribution) and IMM (Municipality of Montevideo).\r\nHe organised Delta ’07 in Calafate, Argentina and he was co-chair of TSG 13 at ICME XII in Seoul, Korea and TSG 16 at ICME XIII in Hamburg, Germany.\r\nHe is a reviewer for several journals as ZDM, IJRUME, iJMEST, ALME (Mexico), Union (Spain) and Numeros (Spain), among others.\r\nHe is part of the Editorial Board for journals like IJRUME and Global Education\r\nReview.\r\nHis main areas of interest are:\r\n• Mathematical modelling\r\n• Inverse problems\r\n• Applied Mathematics in Chemical and/or Environmental problems\r\n• Maths problems in Electrochemistry and corrosion\r\n• Chemical Kinetics\r\n• Electrochemistry\r\n• Environmental problems\r\n• Corrosion",institutionString:null,institution:{name:"University of the Republic",institutionURL:null,country:{name:"Uruguay"}}},{id:"114848",title:"Dr.",name:"Alexandre",surname:"Keiko",slug:"alexandre-keiko",fullName:"Alexandre Keiko",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"115785",title:"Prof.",name:"Boris",surname:"Kaganovich",slug:"boris-kaganovich",fullName:"Boris Kaganovich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Melentiev Energy Systems Institute",institutionURL:null,country:{name:"Russia"}}},{id:"115786",title:"Dr.",name:"Vitaly",surname:"Shamansky",slug:"vitaly-shamansky",fullName:"Vitaly Shamansky",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Melentiev Energy Systems Institute",institutionURL:null,country:{name:"Russia"}}},{id:"115787",title:"MSc.",name:"Maxim",surname:"Zarodnyuk",slug:"maxim-zarodnyuk",fullName:"Maxim Zarodnyuk",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Melentiev Energy Systems Institute",institutionURL:null,country:{name:"Russia"}}}]},generic:{page:{slug:"WIS-cost",title:"What Does It Cost?",intro:"
Open Access publishing helps remove barriers and allows everyone to access valuable information, but article and book processing charges also exclude talented authors and editors who can’t afford to pay. The goal of our Women in Science program is to charge zero APCs, so none of our authors or editors have to pay for publication.
",metaTitle:"What Does It Cost?",metaDescription:"Open Access publishing helps remove barriers and allows everyone to access valuable information, but article and book processing charges also exclude talented authors and editors who can’t afford to pay. The goal of our Women in Science program is to charge zero APCs, so none of our authors or editors have to pay for publication.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"
We are currently in the process of collecting sponsorship. If you have any ideas or would like to help sponsor this ambitious program, we’d love to hear from you. Contact us at info@intechopen.com.
\\n\\n
All of our IntechOpen sponsors are in good company! The research in past IntechOpen books and chapters have been funded by:
\\n\\n
\\n\\t
European Commission
\\n\\t
Bill and Melinda Gates Foundation
\\n\\t
Wellcome Trust
\\n\\t
National Institute of Health (NIH)
\\n\\t
National Science Foundation (NSF)
\\n\\t
National Institute of Standards and Technology (NIST)
We are currently in the process of collecting sponsorship. If you have any ideas or would like to help sponsor this ambitious program, we’d love to hear from you. Contact us at info@intechopen.com.
\n\n
All of our IntechOpen sponsors are in good company! The research in past IntechOpen books and chapters have been funded by:
\n\n
\n\t
European Commission
\n\t
Bill and Melinda Gates Foundation
\n\t
Wellcome Trust
\n\t
National Institute of Health (NIH)
\n\t
National Science Foundation (NSF)
\n\t
National Institute of Standards and Technology (NIST)
\n\t
Research Councils United Kingdom (RCUK)
\n\t
Foundation for Science and Technology (FCT)
\n\t
Chinese Academy of Sciences
\n\t
Natural Science Foundation of China (NSFC)
\n\t
German Research Foundation (DFG)
\n\t
Max Planck Institute
\n\t
Austrian Science Fund (FWF)
\n\t
Australian Research Council (ARC)
\n
\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:{hasNoEditors:"0",sort:"ebgfFaeGuveeFgfcChcyvfu"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:16},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:4},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:8},{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:16},{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:26},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:1},{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:0,limit:12,total:null},popularBooks:{featuredBooks:[],offset:0,limit:12,total:null},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:"120",title:"Knowledge Engineering",slug:"engineering-knowledge-engineering",parent:{title:"Engineering",slug:"engineering"},numberOfBooks:1,numberOfAuthorsAndEditors:2,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfDimensionsCitations:2,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"engineering-knowledge-engineering",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"6449",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",subtitle:null,isOpenForSubmission:!1,hash:"130d15f6e439fa4a07b8e8cd9066d5b3",slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",bookSignature:"Jaromir Gottvald and Petr Praus",coverURL:"https://cdn.intechopen.com/books/images_new/6449.jpg",editedByType:"Edited by",editors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,mostCitedChapters:[{id:"57112",doi:"10.5772/intechopen.71098",title:"Traffic Management by Admission Control in IMS Networks",slug:"traffic-management-by-admission-control-in-ims-networks",totalDownloads:519,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Ivan Baroňák, Michal Čuba, Chien-Ming Chen and Ladislav Beháň",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57132",doi:"10.5772/intechopen.71099",title:"Prepaid Voice Services Based on OpenBTS Platform",slug:"prepaid-voice-services-based-on-openbts-platform",totalDownloads:974,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Ladislav Behan, Lukas Orcik, Filip Rezac, Ivan Baronak and Jerry\nChun Wei Lin",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57256",doi:"10.5772/intechopen.71333",title:"Influence of Chroma Subsampling on Objective Video Quality Assessment for High Resolutions",slug:"influence-of-chroma-subsampling-on-objective-video-quality-assessment-for-high-resolutions",totalDownloads:626,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Miroslav Uhrina, Juraj Bienik and Peter Kortis",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]}],mostDownloadedChaptersLast30Days:[{id:"57132",title:"Prepaid Voice Services Based on OpenBTS Platform",slug:"prepaid-voice-services-based-on-openbts-platform",totalDownloads:968,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Ladislav Behan, Lukas Orcik, Filip Rezac, Ivan Baronak and Jerry\nChun Wei Lin",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57114",title:"New Features of Labor Market and Their Impact in China",slug:"new-features-of-labor-market-and-their-impact-in-china",totalDownloads:661,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Yajun Meng",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57256",title:"Influence of Chroma Subsampling on Objective Video Quality Assessment for High Resolutions",slug:"influence-of-chroma-subsampling-on-objective-video-quality-assessment-for-high-resolutions",totalDownloads:622,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Miroslav Uhrina, Juraj Bienik and Peter Kortis",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57128",title:"Employing Monitoring System to Analyze Incidents in Computer Network",slug:"employing-monitoring-system-to-analyze-incidents-in-computer-network",totalDownloads:771,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Lukáš Macura, Jan Rozhon and Jerry Chun-Wei Lin",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57112",title:"Traffic Management by Admission Control in IMS Networks",slug:"traffic-management-by-admission-control-in-ims-networks",totalDownloads:513,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Ivan Baroňák, Michal Čuba, Chien-Ming Chen and Ladislav Beháň",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57130",title:"Mobile Probe for Cellular Network Coverage and Quality Measurement",slug:"mobile-probe-for-cellular-network-coverage-and-quality-measurement",totalDownloads:818,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"David Vasicek, Martin Mikulec, Erik Gresak, Filip Rezac and Erik\nChromy",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57131",title:"Influence of Bit Depth on Objective Video Quality Assessment for High Resolutions",slug:"influence-of-bit-depth-on-objective-video-quality-assessment-for-high-resolutions",totalDownloads:680,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Juraj Bienik, Miroslav Uhrina and Peter Kortis",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57257",title:"The Way of Building Human Capital in China",slug:"the-way-of-building-human-capital-in-china",totalDownloads:594,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Małgorzata Wróblewska and Maria Bernat",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57129",title:"Review of Applying European Option Pricing Models",slug:"review-of-applying-european-option-pricing-models",totalDownloads:730,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Haochen Guo",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]},{id:"57113",title:"Study of Admission Control Methods for IPTV Services",slug:"study-of-admission-control-methods-for-iptv-services",totalDownloads:599,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"proceedings-of-the-3rd-czech-china-scientific-conference-2017",title:"Proceedings of the 3rd Czech-China Scientific Conference 2017",fullTitle:"Proceedings of the 3rd Czech-China Scientific Conference 2017"},signatures:"Erik Chromy, Tsu-Yang Wu, Roman Cipov, Matej Kavacky, Stanislav\nKlucik, Ivan Baronak and Lukas Orcik",authors:[{id:"200987",title:"Prof.",name:"Jaromir",middleName:null,surname:"Gottvald",slug:"jaromir-gottvald",fullName:"Jaromir Gottvald"}]}],onlineFirstChaptersFilter:{topicSlug:"engineering-knowledge-engineering",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/111543/hiroshi-kawanabe",hash:"",query:{},params:{id:"111543",slug:"hiroshi-kawanabe"},fullPath:"/profiles/111543/hiroshi-kawanabe",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)}()