Polymers used for imprinting and its glass transition temperature.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"9722",leadTitle:null,fullTitle:"Milk Substitutes - Selected Aspects",title:"Milk Substitutes",subtitle:"Selected Aspects",reviewType:"peer-reviewed",abstract:"This book presents certain aspects of the consumer, nutritional, and technological approach to plant-based milk substitutes. It also provides a useful overview of cow’s milk substitutes produced from raw materials along with their composition and quality, shelf life, nutritional value, human health significance, and consumer acceptance. Nutrition issues and consumer acceptance of plant-based foods are extremely important, especially for vegans or individuals with allergy and intolerance issues. These issues are also important for the agriculture industry in developing countries, as they also apply to feed farm animals.",isbn:"978-1-83880-768-9",printIsbn:"978-1-78985-637-8",pdfIsbn:"978-1-83880-769-6",doi:"10.5772/intechopen.87527",price:119,priceEur:129,priceUsd:155,slug:"milk-substitutes-selected-aspects",numberOfPages:136,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"cc91d4cfca40c9ba47bbe34b2f8e8a3e",bookSignature:"Małgorzata Ziarno",publishedDate:"March 24th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9722.jpg",numberOfDownloads:3208,numberOfWosCitations:2,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:11,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:19,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 23rd 2020",dateEndSecondStepPublish:"July 14th 2020",dateEndThirdStepPublish:"September 12th 2020",dateEndFourthStepPublish:"December 1st 2020",dateEndFifthStepPublish:"January 30th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"303881",title:"Prof.",name:"Małgorzata",middleName:null,surname:"Ziarno",slug:"malgorzata-ziarno",fullName:"Małgorzata Ziarno",profilePictureURL:"https://mts.intechopen.com/storage/users/303881/images/system/303881.jpeg",biography:"Małgorzata Ziarno is a professor at the Institute of Food Sciences, Warsaw University of Life Sciences (SGGW-WULS), Poland. Her professional interests include production systems and quality of dairy products and their plant substitutes, analysis and evaluation of dairy products and their plant substitutes, food production hygiene and food quality control, application of lactic acid bacteria and propionic acid bacteria in food production and bioprotection, production of functional food, and modifying the nutritional value. Privately, she is a person with a wide range of interests and a wealth of hobbies, including food, cultivation of plants, astronomy, and cosmonautics as well as music and computer games.",institutionString:"Warsaw University of Life Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Warsaw University of Life Sciences",institutionURL:null,country:{name:"Poland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"323",title:"Food and Nutrition",slug:"food-and-nutrition"}],chapters:[{id:"73915",title:"Plant-Based Milk Substitutes: Factors to Lead to Its Use and Benefits to Human Health",doi:"10.5772/intechopen.94496",slug:"plant-based-milk-substitutes-factors-to-lead-to-its-use-and-benefits-to-human-health",totalDownloads:640,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The consumption of vegetable milk has grown in recent years. Medical reasons are some reasons for the increase in the number of consumers of this type of drink. Lactose intolerance and allergy to cow’s milk protein are the major factors that lead to this consumption in addition to the option for a healthier lifestyle, there are also consumers concerned with animal health and welfare who are adept at restrictive diets like vegetarianism and veganism. Vegetable extracts are water-soluble extracts from legumes, oilseeds, cereals, or pseudocereals that resemble bovine milk in appearance, are considered substitutes for cow’s milk due to the similar chemical composition and can also be used as substitutes for direct use or in some animal milk-based preparations. In contrast, these substitutes have different sensory characteristics, stability, and nutritional composition of cow’s milk. Plant extracts have health-beneficial compounds, phenolic compounds, unsaturated fatty acids, antioxidant activity and bioactive compounds such as phytosterols and isoflavones making plant-based milk substitutes an interesting choice.",signatures:"Laís Zandona, Caroline Lima and Suzana Lannes",downloadPdfUrl:"/chapter/pdf-download/73915",previewPdfUrl:"/chapter/pdf-preview/73915",authors:[{id:"160554",title:"Dr.",name:"Suzana",surname:"Lannes",slug:"suzana-lannes",fullName:"Suzana Lannes"},{id:"334091",title:"Ms.",name:"Laís",surname:"Zandona",slug:"lais-zandona",fullName:"Laís Zandona"},{id:"334092",title:"Ms.",name:"Caroline",surname:"Lima",slug:"caroline-lima",fullName:"Caroline Lima"}],corrections:null},{id:"73738",title:"Production and Consumer Acceptance of Millet Beverages",doi:"10.5772/intechopen.94304",slug:"production-and-consumer-acceptance-of-millet-beverages",totalDownloads:398,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:1,abstract:"The use of millet for the production of plant-based beverages has beneficial effects because it is healthy and gluten-free. In its raw form, millet is rich in dietary fiber and polyphenols. Millet beverages are characterized by relatively low popularity among the consumers of plant beverages. This is mainly due to the drawbacks, namely the presence of plant flavors and “millet” smell. Constant market growth requires new products to be developed in order to meet the consumers’ expectations. The acceptance of millet beverages significantly increases when these are offered in various flavors. Furthermore, the addition of apple or banana puree to millet recipes can increase their desirability. Stabilization of millet beverages is important as they have the tendency to delaminate. This can be overcome by the use of natural stabilizers such as pectin and agar-agar which seems to be an effective option for these products.",signatures:"Patrycja Cichońska and Małgorzata Ziarno",downloadPdfUrl:"/chapter/pdf-download/73738",previewPdfUrl:"/chapter/pdf-preview/73738",authors:[{id:"327238",title:"Prof.",name:"Małgorzata",surname:"Ziarno",slug:"malgorzata-ziarno",fullName:"Małgorzata Ziarno"},{id:"327512",title:"M.Sc.",name:"Patrycja",surname:"Cichońska",slug:"patrycja-cichonska",fullName:"Patrycja Cichońska"}],corrections:null},{id:"75536",title:"Stability Aspects of Non-Dairy Milk Alternatives",doi:"10.5772/intechopen.96376",slug:"stability-aspects-of-non-dairy-milk-alternatives",totalDownloads:527,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"In recent years, plant-based milk products, commonly called as non-dairy milk alternatives have gained high popularity due to concerns associated with bovine milk like lactose intolerance, allergies, hypercholesterolemia, and pesticide and antibiotic residues. Important strategies for manufacture of non-dairy milk alternatives involve disintegration of plant materials in aqueous medium; its homogenization and addition of some additives to attain a consistency and appearance similar to that of bovine milk. Different range of ingredients are added to non-dairy milk alternatives such as oils, emulsifiers, thickeners, antioxidants, minerals etc. The main problem associated with non-dairy milk alternatives is generally linked with its stability. Stability is a crucial factor that governs the sensory properties and overall acceptance of non-dairy milk alternatives. Differences in processing parameters and molecular interaction mechanisms affect the stability of emulsions as well as the stability of non-dairy milk manufactured thereof. Various treatments like thermal treatment, non-thermal processing (ultra high pressure homogenization, pulsed electric field, ultrasonication), addition of emulsifiers are effective in achieving the stability of non-dairy milks. The present chapter aims to summarize the various factors contributing to the physical stability of non-dairy milk alternatives like appearance, consistency, emulsion stability, and the approaches required to maintain it.",signatures:"Jyotika Dhankhar and Preeti Kundu",downloadPdfUrl:"/chapter/pdf-download/75536",previewPdfUrl:"/chapter/pdf-preview/75536",authors:[{id:"325377",title:"Dr.",name:"Jyotika",surname:"Dhankhar",slug:"jyotika-dhankhar",fullName:"Jyotika Dhankhar"},{id:"345217",title:"Ms.",name:"Preeti",surname:"Kundu",slug:"preeti-kundu",fullName:"Preeti Kundu"}],corrections:null},{id:"73613",title:"Kenaf (Hibiscus cannabinus L.) Seed Extract as a New Plant-Based Milk Alternative and Its Potential Food Uses",doi:"10.5772/intechopen.94067",slug:"kenaf-em-hibiscus-cannabinus-em-l-seed-extract-as-a-new-plant-based-milk-alternative-and-its-potenti",totalDownloads:569,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Kenaf (Hibiscus cannabinus L.) seed is rich in protein, fat, fiber, and other essential nutrients. Kenaf seed comprises of high protein (22–31%) and oil (22–25%) contents which suggested its high potential food application. This chapter discusses the potential and early development of kenaf-based plant-milk and tofu. The step-by-step processes involved in preparation of kenaf-based milk and kenaf-based tofu at laboratory-scale are illustrated. Soaking conditions (temperature and time) of kenaf seed as pretreatment in preparation of kenaf seed milk were highlighted. Hydration of kenaf seed were found to be faster at elevated temperature, however higher soaking temperature and prolonged soaking time causes some losses of protein (%) and solid content (%) which are unfavorable for production of highly nutritious plant-based milk. Furthermore, in preparation of kenaf-based tofu, soaking temperature of seed also affected the properties of the tofu. As the soaking temperature was increased from 25–65°C, the yield, hardness, and chewiness of kenaf tofu decreased. It was recommended that soaking of kenaf seed at 25°C and the use of aluminum potassium salt at 1.00 g% as coagulant produces kenaf-based tofu with optimum quality.",signatures:"Roselina Karim, Nor Aini Mat Noh, Shafa’atu Giwa Ibrahim, Wan Zunairah Wan Ibadullah, Norhasnida Zawawi and Nazamid Saari",downloadPdfUrl:"/chapter/pdf-download/73613",previewPdfUrl:"/chapter/pdf-preview/73613",authors:[{id:"220580",title:"Prof.",name:"Nazamid",surname:"Saari",slug:"nazamid-saari",fullName:"Nazamid Saari"},{id:"326681",title:"Associate Prof.",name:"Roselina",surname:"Karim",slug:"roselina-karim",fullName:"Roselina Karim"},{id:"330943",title:"Ms.",name:"Nor Aini",surname:"Mat Noh",slug:"nor-aini-mat-noh",fullName:"Nor Aini Mat Noh"},{id:"330950",title:"Mrs.",name:"Shafa'Atu Giwa",surname:"Ibrahim",slug:"shafa'atu-giwa-ibrahim",fullName:"Shafa'Atu Giwa Ibrahim"},{id:"331393",title:"Dr.",name:"Wan Zunairah",surname:"Wan Ibadullah",slug:"wan-zunairah-wan-ibadullah",fullName:"Wan Zunairah Wan Ibadullah"},{id:"331395",title:"Dr.",name:"Norhasnida",surname:"Zawawi",slug:"norhasnida-zawawi",fullName:"Norhasnida Zawawi"}],corrections:null},{id:"74166",title:"The Possibility of Obtaining Buckwheat Beverages Fermented with Lactic Acid Bacteria and Bifidobacteria",doi:"10.5772/intechopen.94913",slug:"the-possibility-of-obtaining-buckwheat-beverages-fermented-with-lactic-acid-bacteria-and-bifidobacte",totalDownloads:425,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this study, we aimed to examine the effect of four different industrial starter cultures containing lactic acid bacteria and bifidobacteria on the selected characteristics of beverages prepared from buckwheat and stored at 4°C for 28 days. We estimated the pH of the beverages during fermentation and storage under refrigerated conditions. We also determined the number of lactic acid bacteria and bifidobacteria and performed a chromatographic analysis of the carbohydrates. According to the results, the tested starter cultures effectively fermented the buckwheat beverage. The viable cell count of the starter microflora was sufficient to demonstrate the health-promoting properties of buckwheat. The pH of beverages was stable during the refrigerated storage. However, the carbohydrate content of the stored beverages changed, which indicates a constant biochemical activity of the microflora.",signatures:"Ewa Kowalska and Małgorzata Ziarno",downloadPdfUrl:"/chapter/pdf-download/74166",previewPdfUrl:"/chapter/pdf-preview/74166",authors:[{id:"327238",title:"Prof.",name:"Małgorzata",surname:"Ziarno",slug:"malgorzata-ziarno",fullName:"Małgorzata Ziarno"},{id:"327231",title:"M.Sc.",name:"Ewa",surname:"Kowalska",slug:"ewa-kowalska",fullName:"Ewa Kowalska"}],corrections:null},{id:"74899",title:"Functional Fermented Beverage Prepared from Germinated White Kidney Beans (Phaseolus vulgaris L.)",doi:"10.5772/intechopen.95818",slug:"functional-fermented-beverage-prepared-from-germinated-white-kidney-beans-em-phaseolus-vulgaris-em-l",totalDownloads:391,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The current demand for plant-based food indicates that the food market is providing alternatives for products that are currently commercially available. This chapter discusses the possible use of germinated bean seeds as a raw material in the production of substitutes for dairy products, including fermented ones. Beans are a valuable source of easily digestible protein, carbohydrates, minerals, and various vitamins (e.g., B vitamin group). They also contain significant amounts of fiber which affects the proper functioning of the digestive system and antioxidant compounds. The fat content is low and is estimated to be around only 1–2%. However, it is mainly (about 70%) constituted by unsaturated fatty acids, including the polyunsaturated ones such as linoleic acid or linolenic acid, which are desirable in the human diet for the prevention of cardiovascular diseases or cancer. Biological processes such as germination or fermentation may improve the nutritional value of bean seeds (by increasing the content, digestibility, and bioavailability of some nutrients and by eliminating undesirable components) and deliver live cells of prohealth bacteria (lactic acid bacteria, propionic acid bacteria, or bifidobacteria).",signatures:"Anna Veber, Dorota Zaręba and Małgorzata Ziarno",downloadPdfUrl:"/chapter/pdf-download/74899",previewPdfUrl:"/chapter/pdf-preview/74899",authors:[{id:"303881",title:"Prof.",name:"Małgorzata",surname:"Ziarno",slug:"malgorzata-ziarno",fullName:"Małgorzata Ziarno"},{id:"327274",title:"Dr.",name:"Anna",surname:"Veber",slug:"anna-veber",fullName:"Anna Veber"},{id:"327275",title:"Dr.",name:"Dorota",surname:"Zaręba",slug:"dorota-zareba",fullName:"Dorota Zaręba"}],corrections:null},{id:"73457",title:"Use of Soy Milk in Lamb Feeding",doi:"10.5772/intechopen.94029",slug:"use-of-soy-milk-in-lamb-feeding",totalDownloads:265,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Soy milk was administered to Djallonké Lambs in pre weaning. Three groups of 20 animals, all from a traditional farming, were performed. Group 1 (control) was deprived of soy milk. In the 2nd and 3rd group lambs received 50 and 100 ml soy milk respectively per head. Food supplementation with soy milk began a week after the lambs’ birth. Soy milk was administered daily at the same time in one meal using a suckling bottle before leaving to the pasture. The results showed a significant delay of growth of the control group compared to the other groups. At the end of the 2nd week, the body weight difference was in average 0.32and 0.42 kg respectively for the control and the two other groups. At the end of the 12th week this difference became 2.55 and 3.22 kg respectively for the control and the two other groups. No significant differences were observed between the live weights’ mean in the 2nd and 3rd group.",signatures:"Youssouf Toukourou and Abdoulaye Moubarack",downloadPdfUrl:"/chapter/pdf-download/73457",previewPdfUrl:"/chapter/pdf-preview/73457",authors:[{id:"325927",title:"Associate Prof.",name:"Youssouf",surname:"Toukourou",slug:"youssouf-toukourou",fullName:"Youssouf Toukourou"},{id:"329619",title:"MSc.",name:"Abdoulaye",surname:"Moubarack",slug:"abdoulaye-moubarack",fullName:"Abdoulaye Moubarack"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"497",title:"Soybean and Nutrition",subtitle:null,isOpenForSubmission:!1,hash:"11aa0c9ed0f6ea8da765be93b50954bb",slug:"soybean-and-nutrition",bookSignature:"Hany El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/497.jpg",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"496",title:"Soybean and Health",subtitle:null,isOpenForSubmission:!1,hash:"66d40dbc031b2825ba95f7ac2bfae1b6",slug:"soybean-and-health",bookSignature:"Hany El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/496.jpg",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1018",title:"Milk Production",subtitle:"An Up-to-Date Overview of Animal Nutrition, Management and Health",isOpenForSubmission:!1,hash:"0666bd242c21546d0c83c0290bd114ea",slug:"milk-production-an-up-to-date-overview-of-animal-nutrition-management-and-health",bookSignature:"Narongsak Chaiyabutr",coverURL:"https://cdn.intechopen.com/books/images_new/1018.jpg",editedByType:"Edited by",editors:[{id:"76047",title:"Prof.",name:"Narongsak",surname:"Chaiyabutr",slug:"narongsak-chaiyabutr",fullName:"Narongsak Chaiyabutr"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2066",title:"Milk Production",subtitle:"Advanced Genetic Traits, Cellular Mechanism, Animal Management and Health",isOpenForSubmission:!1,hash:"0bce9f57b06503666b182457b414a9de",slug:"milk-production-advanced-genetic-traits-cellular-mechanism-animal-management-and-health",bookSignature:"Narongsak Chaiyabutr",coverURL:"https://cdn.intechopen.com/books/images_new/2066.jpg",editedByType:"Edited by",editors:[{id:"76047",title:"Prof.",name:"Narongsak",surname:"Chaiyabutr",slug:"narongsak-chaiyabutr",fullName:"Narongsak Chaiyabutr"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6678",title:"Antioxidants in Foods and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"819eb2d8d2c889ef23affd7fd01e4e98",slug:"antioxidants-in-foods-and-its-applications",bookSignature:"Emad Shalaby and Ghada Mostafa Azzam",coverURL:"https://cdn.intechopen.com/books/images_new/6678.jpg",editedByType:"Edited by",editors:[{id:"63600",title:"Prof.",name:"Emad",surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6669",title:"Meat Science and Nutrition",subtitle:null,isOpenForSubmission:!1,hash:"bca2d87ed258a60a9c92c5c6056d1465",slug:"meat-science-and-nutrition",bookSignature:"Muhammad Sajid Arshad",coverURL:"https://cdn.intechopen.com/books/images_new/6669.jpg",editedByType:"Edited by",editors:[{id:"192998",title:"Dr.",name:"Muhammad Sajid",surname:"Arshad",slug:"muhammad-sajid-arshad",fullName:"Muhammad Sajid Arshad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6155",title:"Diabetes Food Plan",subtitle:null,isOpenForSubmission:!1,hash:"b826ff12304ae270954a41210f4e1582",slug:"diabetes-food-plan",bookSignature:"Viduranga Waisundara",coverURL:"https://cdn.intechopen.com/books/images_new/6155.jpg",editedByType:"Edited by",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. 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Kumavath and Pratap Deverapalli",dateSubmitted:"October 10th 2012",dateReviewed:"March 18th 2013",datePrePublished:null,datePublished:"October 2nd 2013",book:{id:"3547",title:"Applied Bioremediation",subtitle:"Active and Passive Approaches",fullTitle:"Applied Bioremediation - Active and Passive Approaches",slug:"applied-bioremediation-active-and-passive-approaches",publishedDate:"October 2nd 2013",bookSignature:"Yogesh B. 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Kumavath and Pratap Deverapalli",dateSubmitted:"October 10th 2012",dateReviewed:"March 18th 2013",datePrePublished:null,datePublished:"October 2nd 2013",book:{id:"3547",title:"Applied Bioremediation",subtitle:"Active and Passive Approaches",fullTitle:"Applied Bioremediation - Active and Passive Approaches",slug:"applied-bioremediation-active-and-passive-approaches",publishedDate:"October 2nd 2013",bookSignature:"Yogesh B. 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\r\n\tCOVID-19 is a rampant worldwide problem. It is caused by the SARS-CoV-2 virus and has manifested into different variants. Previously, the delta variant has compromised existing therapeutic and preventive options for this disease. Now, the omicron variant is beginning to replace the others. In this respect, strategies to treat and cure COVID-19 should be devised. In the light of pharmaceutical biotechnology, three different approaches could be catered to resolve this issue. First, Computer-Aided Drug Design (CADD) approach. Second, rational drug design in the wet lab approach. Third, is the advanced drug delivery system. These approaches are influenced heavily by advances in life sciences such as the inception of structural bioinformatics as an independent study, the establishment of nanobiotechnology as a standard approach in drug design, and high advancement in structural biology such as the development of the CryoEM method. This book will focus on providing possible solutions toward this ongoing COVID-19 pandemic, in the light of those advancements in life sciences.
",isbn:"978-1-80356-990-1",printIsbn:"978-1-80356-989-5",pdfIsbn:"978-1-80356-991-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"f8092a491f68ca0b63cc6d40936a010a",bookSignature:"Dr. Arli Aditya Parikesit",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11690.jpg",keywords:"Molecular Docking, Molecular Dynamics, Biomolecular Modeling, Homology Modeling, In Vitro Drug Testing, In Vivo Drug Testing, Structural Biology, Nano Delivery, Prodrug, Smart Drug, Liposome, Wet Lab",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 12th 2022",dateEndSecondStepPublish:"June 22nd 2022",dateEndThirdStepPublish:"August 21st 2022",dateEndFourthStepPublish:"November 9th 2022",dateEndFifthStepPublish:"January 8th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A researcher in transcriptomics, immunoinformatics, and structural bioinformatics, ISBB and APBIONET member, currently involved in COVID-19 Drug and Vaccine design. Dr. Parikesit was awarded his Ph.D. from the University of Leipzig, was previously affiliated with the University of Indonesia, and acted as a reviewer for the American Journal of applied sciences, American Journal of molecular biology, and Indonesian Journal of Biotechnology.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",slug:"arli-aditya-parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",biography:"Dr. rer. nat. Arli Aditya Parikesit is the Vice Rector of Research and Innovation at Indonesia International Institute for Life Sciences (I3L). He finished both his bachelor’s and master’s degrees in chemistry at the Faculty of Mathematics and Natural Sciences, University of Indonesia. In order to pursue a degree in Bioinformatics, he accepted an offer from DAAD (German Academic Exchange Service) to conduct doctorate research at the Bioinformatics Group, Faculty of Informatics and Mathematics, University of Leipzig, Germany. His doctoral research is focused on the utilization of modern protein domain annotation techniques to the three domains of life. In addition, Dr. Arli is also an expert on immunoinformatics, bioinformatics algorithm, structural bioinformatics, in silico drug design, and in silico transcriptomics. 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Since 1990´s, one of the imprinting techniques, i.e., injection moulding has been used for compact disk (CD) production. More recently, the semiconductor industry is interested in imprint related techniques because of the mass production requirement of future microelectronic circuits with a possible critical dimension down to a few nanometers. At this deep nanometer scale, traditional photolithography is supposed to rule out because of the optical diffraction or material limitations. In fact, the actual minimum feature size in an integrated circuit (IC) is already less than 50 nm and the actual manufacturing systems are already extremely sophisticated and expensive. The semiconductor industry has always been looking for alternative patterning methods in order to follow Moore´s law, which has been formulated to predict the evolution of the technology nodes. Now, extreme UV lithography (EUV), 193 nm immersion lithography, mask less lithography (MLL) techniques and nanoimprint lithography (NIL) are considered as candidates for the so called
The history of imprint technology as lithography method for pattern replication can be traced back to 1970’s but the most significant progress has been made by the research group of S. Chou in the 1990’s. Since then, it has become a popular technique with a rapidly growing interest from both research and industrial sides and a variety of new approaches have been proposed along the mainstream scientific advances. Indeed, the initial proposal of Chou et al. has been made for the mass production of high density magnetic storage media and it has been used to demonstrate the feasibility of all kind of fine structure patterning at a nanometer scale resolution which is now called nanoimprint lithography.
\n\t\t\tNanoimprint lithography is based on surface structuring with a template consisting of topographic patterns. After imprinting, the patterns have to be transferred in order to obtain different functionalities. As lithography method, nanoimprint is fully compatible to the standard micro-fabrication techniques, including different transfer processes such as etching, lift-off, selective re-growth or diffusion. In most cases, a thin layer of resist is deposited on the substrate and then imprinted, resulting in a thickness contrast. This may need a further treatment by reactive ion etching (RIE) to remove the residual resist layer and to transfer the features into the used substrate material. Therefore, the process control of both imprinting and etching are important in order to obtain a suitable resist profile without any residual layer. For some particular applications, the resist layer can be replaced by functional materials or omitted for an imprint directly into the substrate.
\n\t\t\tCurrently, two main types of nanoimprint methods are existing, i.e., hot embossing and UV-based nanoimprint lithography (UV-NIL). An overview of the most important nanoimprinting techniques and its related stamp materials is shown in figure 1. Thermal processing has been demonstrated by S. Chou et al., which consists of deforming a thermoplastic polymer layer such as a polymer (e.g. PMMA, COC, PC) spin coated on a substrate or a polymer substrate. After pre-bake and heating up above the glass transition temperature of the polymer, the imprint is performed by applying a contact force on the stack consisting of template and substrate. Then, the template-substrate assembly is cooled down before the template release. Alternatively, the UV-based technique is based on the use of photo-curable resist, which can be easily deformed at room temperature and cured by UV-light exposure. Thus the main difference between the two techniques are the material types of both template and resist, i.e., transparent templates and photosensitive resists for UV-NIL, but in some cases non-transparent templates and thermoplastic resists for thermal-NIL.
\n\t\t\tFor both hot embossing and UV-based processes, the template fabrication is one of the most critical issues because of its high cost. This depends on the required minimum feature size, the density of the features and the patterned area. In general, electron beam lithography and reactive ion etching are used to pattern silicon or quartz glass wafers. High resolution patterning over a large wafer area is time consuming but ideally, once the template has been produced, it can be used for many times. In practice, both silicon and quartz glass templates can be damaged due to process imperfection.
\n\t\t\tCompared to hot embossing, UV-NIL is advantageous when multi-level patterning is needed due to the fact, that high precision alignment can be done much easier with processes performed at room temperature as there are no thermal gradients generated. Basically, the cycle time of UV-NIL is shorter than in hot embossing due to the absence of heating and cooling cycles (heating-up to the imprinting temperature and cooling down to the de-embossing temperature). In addition, both pattern placement accuracy and overlay alignment accuracy of UV-NIL are also inherently higher than in hot embossing processes, because of reduced size variations of templates and wafer materials due to the thermal cycles. It is known that with an increase of the wafer size, the wafer flatness decreases so that a high pressure has to be applied to assure a good imprinting uniformity. Typically, the maximum imprinting area is limited to about 25 mm 25 mm for UV-NIL processes, considering the stiffness and the thickness variations of quartz glass templates and silicon wafers. In particular cases, the step-and-repeat strategy can be applied to replicate the same small sized template many times over the whole wafer area. However, this requires a more sophisticated imprint tool and can not be applied to the general case of large wafer pattern replication. On the other hand hot embossing is superior over UV-NIL if polymer materials need to be imprinted directly.
\n\t\t\tThus, it is highly desirable to have a low cost solution for large area replications, with less risk of template damage but improved process latitude. One possibility is to use soft templates, which are referred to soft working stamps. The use of soft materials should allow for a more conformable imprinting over a large wafer area. Accordingly, soft and hard UV-NIL refers to the material hardness of the template material, hard for a quartz glass template and soft for a soft layer attached to a glass back plane (soft UV-NIL). Another advantage is that such soft working stamps can be easily obtained by casting and curing a liquid precursor of a soft stamp material onto a silicon master. One of the most widely used materials is polydimethylsiloxane (PDMS). The working stamp fabrication is carried out in the same way as the stamp fabrication for micro-contact printing applications. PDMS stamps have a good optical transparency to the wavelengths used for curing of the UV-NIL resists (between 350 nm and 450 nm) and a low surface energy which ensures an easy separation from the substrate after the UV-NIL process. The drawback of PDMS as a soft stamp material for UV-NIL is that due to the low Young’s module of PDMS extremely high resolution pattern in the sub-50 nm range might not be achievable and the local pattern deformation is more critical than in hard UV-NIL. Other materials like perfluorpolyethers (PFPE´s) can be used instead of PDMS for resolving features in the sub-50 nm range.
\n\t\t\tIn this chapter, we are presenting a general process consideration based on the used materials and equipment concepts. The two most important nanoimprint lithography techniques hot embossing and UV-NIL are described in detail with application examples.
\n\t\t\tThis present book chapter focuses on the principles and technologies of hot embossing and UV-NIL structuring techniques; micro contact printing (µ-CP), also considered as soft lithography, is only mentioned in the introduction and is not considered in subsequent paragraphs. Application pictures are added in various sub-chapters to substantiate the described processes.
\n\t\t\tMain nanoimprint lithography techniques with corresponding stamp materials.
The relevant process parameters used for a nanoimprint lithography process strongly depend on the applied nanoimprint technique. On the one hand hot embossing requires high temperatures and high contact forces, whereas in UV-based NIL processes the imprinted monomer or oligomer is cured by UV-light exposure. A basic process flow of a nanoimprinting process independent on the used technique is demonstrated in figure 2. In case of a hot embossing process using a polymer substrate to be imprinted, the structures are directly transferred into the polymer without any resist and pattern transfer process. A resist is either spin coated or droplet dispensed on a substrate. The template is getting in contact with the resist and distributing the resist evenly in case of droplet dispense. The features on the template are structuring the resist surface in a way that the resist is flowing into the cavities of the topography of the template. Curing of the resist is performed by either cooling down below the glass transition temperature of the resist in case of an HE process or by UV-light exposure in an UV-NIL process. The residual resist layer remaining underneath the elevated features of the template has to be removed in a dry reactive ion etching (DRIE) process in order to transfer the pattern into the substrate by either proceeding with the DRIE process used for the resist removal or by applying a different DRIE process. The alignment keys represented on the template and the substrate surface are used if an aligned imprinting process is required. The structuring process is finished by removing the remaining resist from the substrate.
\n\t\t\tGraphical representation of an UV-NIL process including pattern transfer.
In hot embossing processes a polymer sheet or a spin-on polymer is heated above its glass transition temperature and imprinted by applying high contact forces. The stamp material is chosen depending on the required feature sizes and the materials involved.
\n\t\t\t\tA typical process flow for hot embossing is depicted in figure 3.
\n\t\t\t\tHot embossing process flow.
The temperatures of top and bottom side heaters are ramped-up above the glass transition temperature of the polymer to be imprinted. In general the imprint temperature is about 20-50 C higher than the glass transition temperature (Tg) of the polymer. Only thermoplastic polymers can be imprinted as they can be dissolved in appropriate solvents for spin coating and are deformable upon the application of contact forces. During the heating time, the hot embossing chamber is evacuated to about 5 mbar. After reaching the imprint temperature of the polymer the contact force is applied. Its amount is dependent on various parameters such as the stamp area, the type of polymer and the feature geometry. The contact force remains applied until the temperature of the heaters reach the de-embossing temperature. This is the temperature level, which allows a reliable and residue-free separation of the stamp from the polymer. The total cycle time for a hot embossing process is strongly dependent on the heating and cooling capabilities of the equipment and is in the order of 3 to 20 minutes. In table 1 a summary of polymers used for hot embossing including the glass transition temperature is listed.
\n\t\t\t\tThe fastest possible hot embossing processes are isothermal processes. In this scenario the imprint temperature and the de-embossing temperature of the substrate are the same. The heaters can remain at the same temperature level all the time. The resist is fluid enough to guarantee a very fast imprint as soon as it gets in contact with the template and the contact force is applied. De-embossing is performed outside of the chamber in this case. Cycle times of 2 minutes have been demonstrated with high resolution features down to 50 nm on a 200 mm Si substrate by using a EVG520HE hot embossing equipment.
\n\t\t\t\tThe following stamp materials are widely used for hot embossing processes:
\n\t\t\t\tPolymer | \n\t\t\t\t\t\t\tShort name | \n\t\t\t\t\t\t\tGlass transition temperature [T g] | \n\t\t\t\t\t\t
Polymer substrates | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t |
Cyclo olefine copolymer | \n\t\t\t\t\t\t\tCOC | \n\t\t\t\t\t\t\t60 ? | \n\t\t\t\t\t\t
Polystyrene | \n\t\t\t\t\t\t\tPS | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
Polymethylmethacrylate | \n\t\t\t\t\t\t\tPMMA | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
Polycarbonate | \n\t\t\t\t\t\t\tPC | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
Spin-on polymers | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t |
mr-I-7000 | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
mr-I-8000 | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
mr-I-9000E | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
mr-I T85 | \n\t\t\t\t\t\t\t- | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
Polymers used for imprinting and its glass transition temperature.
Silicon
Fused quartz glass
Nickel
Soft working stamps
\n\t\t\t\t\tTable 2 lists commonly used stamp materials for hot embossing including the fabrication process, the type of hot embossing process, the thermal expansion of the stamp material as well as its required surface treatment prior to imprinting. The corresponding thermal expansion coefficient plays a role in case of optical alignment is required. In order to achieve optimized alignment conditions, the thermal expansion of template and substrate should be matched.
\n\t\t\t\tStamp material for hot embossing | \n\t\t\t\t\t\t\tFabrication process | \n\t\t\t\t\t\t\tHot embossing process type | \n\t\t\t\t\t\t\tThermal expansion [10 -6 K -1 ] | \n\t\t\t\t\t\t\tSurface treatment | \n\t\t\t\t\t\t
Silicon | \n\t\t\t\t\t\t\te-beam, optical lithography, | \n\t\t\t\t\t\t\tSpin-on layer | \n\t\t\t\t\t\t\t2.6 | \n\t\t\t\t\t\t\tSilane | \n\t\t\t\t\t\t
Fused quartz glass | \n\t\t\t\t\t\t\te-beam | \n\t\t\t\t\t\t\tSpin-on layer | \n\t\t\t\t\t\t\t0.6 | \n\t\t\t\t\t\t\tSilane | \n\t\t\t\t\t\t
Nickel | \n\t\t\t\t\t\t\tOptical lithography, electroplating | \n\t\t\t\t\t\t\tPolymer sheet | \n\t\t\t\t\t\t\t13 | \n\t\t\t\t\t\t\tNot required | \n\t\t\t\t\t\t
Soft working stamps | \n\t\t\t\t\t\t\tReplication from a Si or SiO 2 master | \n\t\t\t\t\t\t\tSpin-on layer, polymer sheet | \n\t\t\t\t\t\t\t310 for PDMS 340 for MD-500 PFPE | \n\t\t\t\t\t\t\tNot required | \n\t\t\t\t\t\t
Stamp materials used for hot embossing and its characteristics.
Soft working stamps can be fabricated from Ni masters, glass masters or directly from resist masters after lithography (e.g. e-beam, optical, laser). In figure 4 the basic process flow of the soft working stamp fabrication process is demonstrated. The liquid pre-cursor of the polymer is dispensed onto the master and squeezed between the master and a glass backplane. Curing of the polymer is achieved by UV-exposure. The soft working stamp attached to the glass backplane is released from the master and represents the reversible image of the master design. The resist master is treated with an anti-sticking layer (fluorinated chemical) in order to ensure a residual-free separation of the polymer from the master. Ni masters are usually not treated as they exhibit good release properties from the master.
\n\t\t\t\tBasic process of soft working stamp fabrication.
In figure 5 and 6 scanning electron microscopy (SEM) pictures of imprinted features are shown replicated by using soft working stamps. In the first case spin-on polymer layers are imprinted whereas in the later case the structures are directly replicated into a polymer.
\n\t\t\t\tSEM images of imprinted features by hot embossing utilizing soft working stamps; left: 50 nm lines, 100 nm high, right: 50 nm and 100 nm meander structures, 100 nm high.
SEM image of 200 µm wide hot embossed micro fluidic channels utilizing working stamp substrate top area.
In UV-based nanoimprint lithography a transparent template with nanostructures on its surface is used to deform a thin resist film or an active material deposited on a substrate followed by a hardening step. The film is cured by photo chemical cross-linking before the stamp is released. When polymer chains are linked together by cross-links, they lose some of their ability to move as individual polymer chains. For example, a liquid polymer (where the chains are freely flowing) can be turned into a "solid" or "gel" by cross-linking the chains together. In polymer chemistry, when a synthetic polymer is cross-linked, it usually means that the entire bulk of the polymer has been exposed to the cross-linking method. The resulting modification of mechanical properties depends strongly on the crosslink density. Low cross-linked densities raise the viscosities of polymers. Intermediate cross-linked densities transform gummy polymers into materials that have elastomeric properties and potentially high strengths. Such materials are usually used as stamp materials. Very high cross-linked densities can cause materials to become very rigid or glassy. Cross-links can be formed by chemical reactions that are initiated by radiation. For example, mixing a non polymerized or partially polymerized resin with specific chemicals called cross-linking reagents results in a chemical reaction that forms cross-links. In hard UV-NIL rigid transparent templates like quartz glass contain the structures whereas in soft UV-NIL polymeric replicas from master templates are used for the imprinting process. Table 3 shows the basic data for both patterning techniques in terms of maximum imprint area and alignment capabilities. Hard- and soft UV-NIL stamps can be re-used many times, in case of hard UV-NIL there is only the need of re-applying the surface release agent called anti sticking layer (ASL), whereas soft stamps are materials with integrated release properties. Soft stamp polymers are cheap and disposable materials, they can be replicated multiple times from the master.
\n\t\t\t\tUV-based imprint lithography can be carried out using different types of imprinting machines: single step, full-field imprinting and step-and-repeat.
\n\t\t\t\tSingle step imprinting machines, like the one shown in figure 7, structure an entire wafer (up to 200 mm) or small areas (called a die) at one time. A step-and-repeat tool (Fig. 8) imprints one die in a hard or soft UV-NIL approach of a wafer at a time and then moves to a new area of the wafer. The process is repeated until the entire wafer is imprinted. One advantage of the step-and-repeat method is that it is easier to achieve a higher alignment accuracy in a smaller area than in a larger area. A second advantage, and probably the most significant for many applications, is that it allows the use of very small hard stamps to create a large imprint
\n\t\t\t\tSingle step semi-automated UV-NIL system.
Step-and-repeat semi-automated UV-NIL system.
area. It is also possible to use such structured areas as large area template for single step imprinting applications.
\n\t\t\t\tNIL has passed the barrier from the laboratory scale to industrial production in various applications such as wafer level camera modules (WLC), optical gratings or LED’s. These applications are described in more detail in the following paragraphs.
\n\t\t\t\t\n\t\t\t\t\t\t\t | Soft Stamps | \n\t\t\t\t\t\t\tHard Stamps | \n\t\t\t\t\t\t
Imprinted area | \n\t\t\t\t\t\t\tUp to | \n\t\t\t\t\t\t\tUp to x 25 mm* | \n\t\t\t\t\t\t
Resist application | \n\t\t\t\t\t\t\tSpin coating, inkjet dispense | \n\t\t\t\t\t\t\tSpin coating, inkjet dispense | \n\t\t\t\t\t\t
Alignment | \n\t\t\t\t\t\t\tAccuracy limited due to distortion of stamp (~ 1 µm) | \n\t\t\t\t\t\t\tHigh precision alignment possible ( < 5 0 nm) | \n\t\t\t\t\t\t
Comparison of soft and hard stamps based on different process parameters.
*in single step imprinting applications
In hard UV-based nanoimprint lithography processes quartz glass templates are used for replication. Due to the thickness variation of substrates and the rigid templates in hard UV-NIL, the area which can be patterned with one imprint step is limited to about 25 mm x 25 mm. Therefore, in order to pattern large substrates up to 300 mm in diameter, a “step-and-repeat” process has to be applied. In soft UV-NIL processes elastomeric stamps are used as they are able to compensate for any surface roughness and curvature of substrates to be imprinted, offering thereby the possibility to pattern at wafer scale with only one imprint step. Hard UV-NIL is preferred over soft UV-NIL for applications demanding high alignment accuracy. Commercially available resist materials have been used such as Amonil from Amo, UVCur21 from micro resist technology and PAK-01 from Toyo Gosei. All these materials can be spin coated on substrates prior to imprinting.
\n\t\t\t\t\tThe adhesion of the resists to the wafer surface has to be increased while the adhesion of the cured resist to the stamp surface has to be as low as possible. In order to get a very low surface energy on the quartz glass template surface an anti-sticking layer (ASL) has to be applied. Silane based ASL´s are covalently bonded onto SiO2 surfaces as shown in figure 9. It has been reported in literature that the anti-sticking layer can be applied in gaseous phase in a vacuum chamber by exclusion of moisture or by simply immersing the template in a
\n\t\t\t\t\tFluorosilanized silicon oxide surface.
liquid ASL and rinse it with solvent. The so called molecular vapor deposition (MVD), proposed by Applied Microstructures, is a room temperature deposition process and takes place in vacuum. Specific chemicals can be deposited on template surfaces such as perfluorodecyltrichlorsilane (FDTS) to serve as hydrophobic coating for the subsequent nanoimprinting process. It was found out empirically that ASL´s deposited from gaseous phase are preferred over liquid deposited films for features sizes smaller than 50 nm.
\n\t\t\t\t\tIn figure 10 an atomic force microscopy (AFM) picture of imprinted sub-µm lines and space features are shown. Figures 11 and 12 demonstrate SEM pictures of imprinted features down to 90 nm resolution using 25 mm x 25 mm quartz glass templates.
\n\t\t\t\t\tThree-dimensional AFM image of an imprinted lines and space structure.
Surface topography investigation - SEM picture of 90 nm imprinted dots (top view).
Cross section investigation - SEM picture of imprinted lines and space structure (chuck tilted by 80 ).
The residual layer and its distribution across the substrate surface is an important characteristic for the subsequent pattern transfer process. It needs to be as thin as possible, usually thinner than 50 nm is requested, and its uniformity should be ± 10% from its average value. Figure 13 shows a cross section SEM picture demonstrating a residual layer thickness of about 50 nm.
\n\t\t\t\t\tClose-up of cross sectional SEM picture of imprinted lines and space structure for residual resist measurement (chuck tilted by 80 ).
Stacking of lines and space structures has been performed by imprinting of features onto SiO2 and pattern transfer into SiO2 with subsequent filling of the etched features with Si. This approach results in 3D photonic crystal woodpile structures exhibiting a full photonic band gap by keeping the required alignment accuracy and the quality of the imprinted layers. In figure 14 all five layers of the Si/SiO2 woodpile structure are shown. The lines and space structures of the first, third and fifth layers are facing towards the observer. The first and fifth layer are above each other and the third layer is shifted by half of the period according to the design rules for the woodpile structure. This is another example where nanoimprint lithography could play a role in the future as manufacturing technique.
\n\t\t\t\t\tSEM picture of 5 layers of the Si/SiO2 woodpile structure.
Templates for nanoimprint lithography are also called stamps or moulds. In case of soft UV-NIL, soft working stamps can be conveniently reproduced by copying from another template which is called master. Silicon masters for soft UV-NIL template replication are fabricated by electron beam lithography, EUV immersion lithography or other high resolution patterning techniques, followed by reactive ion etching and surface coating with a release agent like mentioned in chapter 2.2.1. Both high resolution lithography and reactive ion etching techniques for silicon processing have been well developed, allowing manufacturing of high resolution (better than 50 nm) and high quality masters. However, the cost of high resolution masters increases rapidly with the wafer size and resolution. It is still a big challenge to cover a large area of a wafer because of throughput limitations. The surface treatment of the master with a release agent is still one of the important research topics, although a large number of recipes or processing protocols have been proposed. Fortunately, soft stamp polymers are materials with low surface energy. They can be easily peeled off after curing from a silicon master, which has been simply coated with FDTS by molecular vapor phase deposition. Now, several companies can provide high resolution silicon masters with feature sizes down to < 20 nm at reasonable prices for standard features such as arrays of gratings, checkerboards, dots and holes. Soft working stamps can be obtained by curing the polymer on a master. It may also be necessary to introduce a carrier for the flexible stamp in order to facilitate handling of the soft working stamp in an imprinting system. Such a carrier can either be integrated during the curing process of the template material or thermally bonded after a plasma surface treatment of both glass and back surface of the soft stamp polymer template. The soft template bonded onto a carrier is detached from the master manually after curing. For more advanced fabrication, they can be obtained with a dedicated high accuracy molding unit, to apply highly uniform and repeatable contact forces to ensure that the residual layer is kept thin. This is crucial to avoid distortions during the imprinting process, especially for high resolution features. Finally, UV-curable soft materials are cross-linked via UV-exposure in the UV-imprinting system.
\n\t\t\t\t\tThe stiffness of the fabricated working stamps can be adjusted by changing the mixture ratio of the base liquid and the curing agent or by changing the molecule end groups in case of UV curable polymers. For high resolution patterning, it is better to use a thin layer of hard polymer bonded on to a softer block. Such a double layer can be obtained by first spin coating the hard layer on the master and then attaching a soft block. After thermal bonding, the soft block can easily be peeled off together with the hard layer. Alternatively, other types of “hard” materials such as PMMA and PFPE can be used for the top layer fabrication, but both attaching and peeling processes are much more delicate. In most cases, a stamp made of a single layer polymer and glass back-plane will be sufficient for the pattern replication of feature sizes between 50 nm and a few micrometers, but the bi-layer template configuration ensures both higher resolution and higher mechanical stability.
\n\t\t\t\t\tThe created soft template usually resembles a negative counterpart from the used master. Nowadays there is also the possibility to replicate positive and negative counterparts from one master design by using different stamp polymers. In contrast to the fabrication of quartz glass templates for hard UV-NIL, where the reproduction by copying is much more difficult, a silicon master for soft UV-NIL can be used for copying of many soft working stamps. Soft working stamps have a relative low surface energy which ensures an easier separation from the substrate after UV-NIL. In addition, because of the inherent properties of the soft materials (elastomers), the risk of mechanical damage of the master is also largely reduced. Therefore, the template cost as well as the processing cost of soft UV-NIL is significantly lower than in other nanoimprint techniques.
\n\t\t\t\t\tSoft UV-NIL can be performed in a very simple manner in R&D environments by running the process manually. However, for sophisticated device fabrication and for achieving reproducible results, dedicated systems are necessary with a better imprinting performance and highly controllable process parameters. In principle, a substrate holder, a template holder and a mechanical system that brings the coated substrate and the soft working stamp into contact and a UV-exposure unit are needed. The flexible and forgiving nature of the soft working stamps compensates for the waviness of the substrate and the working stamp itself in order to get full-field highly homogeneous patterns. However, a wedge compensation process has to be performed to ensure that the working stamp and the substrate are parallel before the imprinting process. In addition to that, the imprint force and exposure dose must be controlled over the whole imprinted area and, a suitable detachment unit must be implemented for highly reproducible process results. Finally, an optical alignment is generally required for multilevel device applications.
\n\t\t\t\t\tWith the rapid growing interest in nanoimprint techniques, commercial systems are now available from several companies. In particular,
IQ aligner for large area soft UV NIL (up to 300 mm).
The EVG620 system mentioned in chapter 2.2.1. is able to perform optical lithography as well as hard and soft UV-NIL for R&D applications for substrate sizes up to 150 mm. The IQ aligner like shown in figure 15 is a dedicated system for large area soft UV-NIL applications up to 300 mm substrate size. The available equipment spectrum reaches from semi-automated configurations for research environments to fully automated systems including automated detachment of stamp and substrate. Such systems are already in use for high volume production.
\n\t\t\t\t\tThe general imprinting process of soft UV-NIL can be described as follows:
\n\t\t\t\t\tA UV-curable resist layer is coated onto a substrate. For coating of the resists several methods like spin coating, spray coating and droplet or puddle dispense can be used. The applied coating technique is heavily dependent if a pattern transfer process has to be carried out, which requires thin residual layers in the range of below 50 nm. Such a requirement can be fulfilled by either spin coating of thin layers to be imprinted or discrete droplet dispense of small volumes depending on the feature size and feature density. If the residual layer does not play any role, such as the polymer layer is part of the functional device, the resist can be thicker. In this case the resist can be applied by puddle dispense.
\n\t\t\t\t\tThen, a soft working stamp is brought into contact with the UV-curable resist layer. After applying the contact force on the stack consisting of template, resist, and substrate, the resist is cured by UV-exposure through the transparent working stamp. Finally, the working stamp is separated from the imprinted substrate, resulting in an imprinted resist layer, which is the negative image of any topography preserved on the stamp surface. Due to the double-negative process (master/soft working stamp and soft working stamp/imprint) the imprinted pattern have the same tone as the master.
\n\t\t\t\t\t\n\t\t\t\t\t\tFigures 16 and 17 show AFM measurements of 50 nm boxes on the master and its replica fabricated by nanoimprint lithography. The two structures show a nearly perfect match in pattern fidelity. There is only a variation of < 5% in horizontal and vertical dimensions.
\n\t\t\t\t\tMaster AFM image of 50 nm dots, 100 nm in height.
Corresponding AFM image of 50 nm replicated dots, 100 nm in height.
Besides the double-negative process (master/soft working stamp and soft working stamp/imprint) there is the possibility, by tuning the stamp polymer, to replicate positive and negative counterpart working stamps from one master design. In this case a second working stamp imprinted from a first working stamp is used to perform the final imprint as shown in Figure 18.
\n\t\t\t\t\tSEM Images of 50 nm boxes in a 3 step counterpart imprint.
To obtain a high quality soft UV-imprint, the material parameters as well as the equipment capabilities need to be optimized. Ideally, resists for soft UV-NIL should exhibit properties like low viscosity, high UV sensitivity and good etch resistivity. Suitable UV-curable resist materials may be organic materials or inorganic/organic composites. Low viscosity materials tend to fill up pattern on the soft working stamp surface faster and are capable to replicate higher resolutions, whereas higher viscosity resists may be used for thick layer fabrication, where no pattern transfer is needed. Finally, high UV sensitivity is required for high speed replication and a good etch selectivity is needed for a high quality pattern transfer. Several companies such as AMO (Germany), Micro resist Technology (Germany), and Toyo Gosei (Japan) have developed resists for commercial uses and most of them allow reaching a high resolution with reasonable exposing time and etching sensitivity to standard reactive ion etching processes.
\n\t\t\t\t\tThe choice of substrates for soft UV-NIL strongly depends on the application. In most cases semiconductor materials such as Si wafers (with or without SiO2 layer) are in use. These substrates are sometimes covered with metals, other semiconductors or ceramics, but the process can also be carried out on polymer substrates depending on the adhesion properties of the material combinations.
\n\t\t\t\t\tThe resolution of a lithographic process is of major importance. In case of soft UV-NIL, the resolution is dependent on both materials (soft polymer stamp, UV-NIL resist) and the performance of the imprinting processes. The resolution achievable is definitely better than 50 nm. Figure 19 illustrates an AFM picture of 35 nm half pitch master structures fabricated by extreme-UV interference lithography (EUV-IL) with the corresponding replicated polymeric stamp in figure 20.
\n\t\t\t\t\tAFM image of 35 nm half pitch EUV-IL master template.
AFM image of corresponding 35 nm half pitch polymeric working stamp.
The unique capability of the soft working stamp to compensate for thickness variations of a given substrate makes it possible to imprint over larger area with high uniformity. Therefore, this technology is an ideal candidate for high throughout and high resolution applications. One key parameter to demonstrate the uniformity of an imprint process is the homogeneity of the residual layer thickness. Other assessment parameters are pattern placement accuracy, overlay accuracy, process latitude, defect density, production rate and cost of ownership of a soft UV-NIL process. However, these are depending on the targeted applications and are different for each application as the variety of possible high volume applications are very broad. Soft UV-NIL is best suited for applications where large areas of continuous pattern need to be fabricated without any stitching error. The ability to pattern over large areas in one imprint step can, for sensor application, be used to provide substrates a “larger” surface by introducing a third dimension on a given area. The process can be performed at room temperature by applying small imprint forces, thus it does not impose additional stress on brittle or heat sensitive substrates.
\n\t\t\t\t\tDue to the flexibility of the template curvatures of the substrate may be neglected, yet for the same reason applications that need high definition alignment in the sub-micron range are hard to realize. Up to now the process has found its way into scientific research domains and production lines in micro-optics (Figure 21) and into prototyping for nanophotonics and biotechnology. It is expected to have additional impact in fabrication of memory devices and in display technology.
\n\t\t\t\t\tmm soft stamp replicated lens wafer and 200 mm stacked wafer level camera module.
All imprinting techniques are based on material (polymer) transportation from the recessed area to the non recessed area or template cavities. It is obvious that, no matter how large the pressure and how hard the template material, imprinting is easier if only local or short distance material transportation is involved. Large distance resist flow or large feature size patterning may introduce large working stamp deformation. Therefore, soft UV-NIL is also best suited for applications where only small size features are replicated. For the device fabrication where both small and large size features have to be replicated, a mix-and-match technique can be applied, i.e., only high resolution features (contact holes, grating, dot and hole matrices, etc.) are patterned by soft UV-NIL and all large features (cavities, channels, pads, etc.) by standard optical lithography methods. Being still highly parallel, cost effective, and fully compatible to the requirement of multilevel device manufacturing, such an approach takes the advantage of soft UV-NIL but avoid its inherent drawback.
\n\t\t\t\t\tProbably the most promising high volume application is the fabrication of next generation high density storage medias with a planned capacity in the range of 1 Tb/in². Since the working stamps can be cost-effectively copied from a master and a hard disc media consists of homogenously distributed high resolution features (tracks for disc track recording as shown in figure 22 or dots for bit patterned media), soft UV-NIL can be an attractive candidate for the large scale mass production.
\n\t\t\t\t\tSEM measurement of 50 nm half pitch imprinted data track features utilizing soft stamp imprint lithography.
SEM image of 350 nm photonic crystal holes, structure depth 600 nm utilizing positive and negative counterpart working stamps.
Finally, the soft UV-NIL technique has been used to demonstrate device integration capability. One example is the fabrication of LED devices with photonic crystals. Figure 23 demonstrates a SEM image of photonic crystals replicated with soft UV NIL.
\n\t\t\t\tThe most significant progress in nanoimprint lithography has been made within the last 10 years. Various imprinting modes have been developed and some of them already reached a mature state for research and development environments. Tremendeous progress was seen in building up the infrastructure for NIL. Templates and related fabrication methods, resists and nanoimprinting equipment are commercially available nowadays. This was supported by the foundation of consortia supporting to enhance the infrastructure in NIL. A good example is NILCom, which was founded in 2004 and which aligns activities around the fabrication process for commercial devices.
\n\t\t\tIn addition, a number of potentially high volume future applications have been demonstrated, showing expected performances not only for high resolution patterning, but also for functional device integration. Imprinted micro lenses on up to 200 mm wafers are already in use in wafer-level optics for digital cameras. There are several nanoimprintingprocess modes available. Depending on the type of imprint material and available equipment either hot embossing or UV-NIL processes can be selected. Both types of processes can be performed with either hard template materials (e.g. Silicon, Quartz glass or Nickel) or soft working stamp materials. All of the described techniques have shown resolution capabilities of better than 50 nm. Hot embossing processes are the preferred process for structuring of polymer substrates directly. For devices with tight requirements on the overlay alignment accuracy hard UV-NIL is preferred. Thermal expansion differences of involved materials do not play any role as this process is performed at room temperature. Comparing to hard UV-NIL processes, soft UV-NIL is advantageous because of the possibility of patterning large area at once. Another benefit of soft UV-NIL is the fact that soft working stamps can be easily replicated from a master and each of them can be used for a large number of pattern replications. The risk of damaging the master due to mechanical means is largely reduced due to the soft properties of the working stamp materials. Considering the available infrastructure and the huge market potential, it can be assumed that a range of industrial applications will be realized by applying nanoimprint lithography processes.
\n\t\tThe authors acknowledge the support from the company EV Group for writing this chapter.
\n\t\tCerebral circulation comprising of both arterial (Figure 1) and venous system (Figure 2), is a complex three-dimensional (3D) anatomical structure. Various textbooks and chapters have thrown light on the cerebral circulation system with multiple images and various sections of it. Despite that, neophytes may still find it difficult to mentally visualize the complex structures by cognitive 3D mapping. Hence, we have created a 3D model of the cerebral circulatory system and have provided it, both on an augmented reality (AR) platform as well as 3D printed models, to aid in the visual and tactile guide while learning and teaching.
Image showing the circle of Willis and its parts.
Image showing the cerebral venous system and its parts.
AR and 3D printed models help in academic-oriented learning of all the cerebral circulation disease conditions and their pathophysiologies [1, 2, 3, 4]. We have created 3D models of the cerebral system comprising of various parts such as the cerebral nervous, venous and arterial system along with the brain, brainstem, and eyeball in fine detail (Figure 3). By creating these models with meticulous detailing and by incorporating them through AR (Figures 4–6), and by 3D printing these models (Figures 7–9), understanding of the disease process is made more serene and undemanding with gameful cognitive learning. Also, complex pathways such as the cranial nerve pathways (Figure 10) are traced in a three-dimensional manner for facilitating easy cognitive reading.
Image showing the 3D model of the cerebral system comprising of various parts such as the cerebral nervous, venous and arterial system along with the eyeball and its components.
Image showing the circle of Willis in the mobile screen over the AR template (red arrow).
Image showing the cerebral venous system in the mobile screen over the AR template.
Image showing the eyeball in the mobile screen over the AR template.
(a) Image showing the 3D printed puzzle pieces of the circle of Willis. (b) Image showing the final assembled model of the circle of Willis, after the puzzle pieces are joined together.
(a) Image showing the 3D printed puzzle pieces of the cerebral venous system. (b) Image showing the final assembled model of the cerebral venous system, after the puzzle pieces are joined together.
(a) Image showing the 3D printed puzzle pieces of the eyeball. (b) Image showing the final assembled model of the eyeball, after the puzzle pieces are joined together.
(a) Image showing the various cranial nervous systems highlighting the (b) 3rd cranial nerve, (c) 4th cranial nerve, (d) 5th cranial nerve, (e) 6th cranial nerve, (f) 7th cranial nerve and (g) 8th cranial nerve respectively in green colour.
Ophthalmologist may be the first responder for detecting the cerebral pathologies earlier, thus helping in faster diagnosis and aiding in speedy treatment. In this chapter, we have discussed the anatomy of various ophthalmology-related cerebral arterial systems from a neophyte’s point of view in detail, with the help of innovative 3D models and animative video created by us, to simplify the concept learning to aid in timely diagnosis and effective management.
The circle of Willis (Figure 1) is a ring of vessels that provides important colligative communications between the anterior and posterior circulations of the midbrain and hindbrain. The communications are established between the carotid and vertebrobasilar systems in conjunction around the optic chiasma and infundibulum of the pituitary stalk in the suprasellar cistern. It is named after Thomas Willis (1621–1675), an English physician [5]. The circle of Willis plays an important role, as it allows proper blood flow from the arteries to both the anterior and posterior hemispheres of the brain, and defends against ischemia in the incident of vessel disease or damage in one or more areas. In the event of arterial incompetency, it also provides collateral arterial flow to the affected brain regions [6, 7, 8].
Vessels comprising the circle of Willis include the following:
Anterior circulation
Posterior circulation
Video 1. Animated video depicting the anatomical structures of circle of Willis. Available from (can be viewed at): https://www.youtube.com/watch?v=yCM0Tq9JiFY
When the right and left internal carotid artery (ICA) enter the cranial cavity, each one divides into two main branches:
Anterior cerebral artery (ACA)
Middle cerebral artery (MCA)
The ring is formed proximally by a single anterior communicating artery (AComA), which links the bilateral ACAs. Each ICA individually gives off an ophthalmic artery. At the junction between the ACA and the ICA, the lateral continuation of the ICA becomes the MCA.
The posterior communicating artery (PComA) arises from each ACA-ICA junction. The PComA connects the MCA with the posterior cerebral artery (PCA), to form the posteriormost aspect of the circle of Willis. The basilar artery (BA) forms from the fusion of the bilateral PCAs. The BA provides many branches, including the superior cerebellar arteries, pontine arteries, and the anterior inferior cerebellar artery (AICA). From the BA emerges bilateral vertebral artery (VA), which each gives of a posterior inferior cerebellar artery (PICA). The BA artery also contributes to the formation of a single anterior spinal artery [9, 10]. The combination of the AComA and the PComA makes up the circle of Willis, which permits collateral flow between the carotid and vertebrobasilar systems when there is vascular compromise.
The ICAs are part of the anterior circulation, which carries major blood supplies to the intracranial contents. There is a total of two ICA; originating from the carotid bifurcation, which runs cephalically through the neck and into the brain. It enters the skull through the carotid canal and reaches the cavernous sinus through the foramen lacerum after passing the parasellar area, and gives off the meningohypophyseal trunk that supplies the dura at the back of the cavernous sinus, as well as the oculomotor, trochlear, trigeminal, and abducens cranial nerves. The ICA makes a loop to reverse its direction under the anterior clinoid and the optic nerve at the anterior aspect of the cavernous sinus and passes through the two dural rings. After passing through the second dural ring, it becomes intradural and gives off the ophthalmic artery which is stemming out from the ophthalmic segment (C6) of the ICA. The ophthalmic artery enters into the orbit through the optic canal. It provides numerous collateral branches to supply the optic nerve. The ophthalmic artery’s first major daughter branch is the central retinal artery which supplies the retina [11]. The ophthalmic artery provides oxygenated blood to the extraocular muscles, some facial muscles, as well as the intrinsic muscles of the eye [12]. Distal to the origin of the ophthalmic artery, the intradural supraclinoid ICA gives rise to the anterior choroidal artery which supplies blood to the lateral geniculate body (LGB) distally and the optic tract proximally. Anterior choroidal artery anastomoses with the PCA through the PComA. The ICA gives off the ACA and ends as a branch of the MCA [13].
The AComA connects the two ACAs across the starting point of the longitudinal fissure, organizing the anterior border of the cerebral arterial circle of Willis. Besides forming the conjugation channel between the anterior cerebral arteries, the AComA also contributes to supplying blood to certain parts of the brain via its anteromedial central branches. This artery supplies parts of the optic chiasma and intracranial optic nerves [14].
The two ACAs are connected by the AComA. The ACA develops from a primitive anterior division of the ICA that initially supplies oxygenated blood to most midline portions of the frontal lobes, and superior, medial, and parietal lobes. The basal branch arising from the lenticulostriate branch of ACA supplies the posterior aspect of the optic chiasma. The cortical branch and orbitofrontal branch of ACA supply the olfactory cortex, gyrus rectus, and medial orbital gyrus [15].
The right and left PComAs form the dorsal part of the circle of Willis, at the base. Each PComA links the three cerebral arteries of the same side. Before the terminal bifurcation of the ICA into the ACA and MCA, the PComA connects to the ICA anteriorly. It links with the PCA posteriorly. The PComA supplies the rear part of the optic chiasma and optic tract [16].
The left and right PCA is a terminal branch that arises from the bifurcation of the BA. The PCA moves around the cerebral peduncle and supplies the occipital lobe, the inferomedial surface of the temporal lobe, midbrain, thalamus, and choroidal plexus of the third and lateral ventricles after passing above the tentorium. The PCA gives off central branches and cortical branches which supplies the subcortical and cortical structures, respectively. The central branches of PCA include the thalamoperforating artery, thalamogeniculate artery, and posterior choroidal artery. The cortical branches of PCA include the temporal artery, occipital artery, parieto-occipital artery, and calcarine artery [17, 18].
The thalamoperforating arteries arise from the P1 segment of PCA and supplies parts of the thalamus, the third ventricles, and the midbrain. The thalamogeniculate artery arises from the P2 segment of PCA and supplies the medial and lateral geniculate bodies and the pulvinar of the thalamus. The medial and lateral posterior choroidal arteries supply the dorsal portion of the thalamus and the choroidal plexus.
The temporal branches are given off from the P2 segment supply the uncus and the parahippocampal, medial, and lateral occipitotemporal gyri. The occipital branches supply the cuneus, lingual gyrus and posterolateral surface of the occipital lobe. The parieto-occipital artery arises from the P3 segment and supplies the cuneus and precuneus. The calcarine artery supplies the visual cortex, inferior cuneus, and part of the lingual gyrus, which arise indirectly from the occipital artery.
The visual cortex responsible for the contralateral field of vision lies in its domain. The macular part of the visual cortex often receives blood supply from both the PCA and MCA. It describes the “macular sparing” phenomenon in some patients following a PCA infarct.
The right VA arises from the innominate artery, and the left VA begins as a branch of the proximal subclavian artery. The VA moves through a series of foramina in the lateral aspect of the cervical vertebral processes. After crossing the dura at the foramen magnum, the VA gives rise to the PICA before linking the other VA to form the BA. Along the course of the BA, small branches arise directly to supply parts of the pons and midbrain. The median branches of the BA supply the medial longitudinal fasciculus, paramedian pontine reticular formation (PPRF), and the medially located nuclei of the oculomotor, trochlear, and abducens nerve. The pontine branch of the BA also supplies the front portions of the cranial nerves (particularly the trigeminal nerve) at the point where they exit from the brainstem. Distally, the PICA supplies the inferior cerebellum, which is closely involved in eye movements. The AICA originates from the caudal BA and supplies the pontomedullary junction and the posterior part of the cerebellum. The internal auditory artery which is a large proximal branch of the AICA supplies the facial cranial nerve complex in the subarachnoid space and follows it into the internal auditory canal [19].
The construction of the cerebral arterial system was done in Maya LT software [3, 20]. The reference image was first taken for the cerebral arterial system to e-trace it using the CV curve tool. Tracing of the different arteries was done using the three orthographic views, namely X-axis, Y-axis and Z-axis (Figure 11). This results in a cerebral arterial system, which is made up of lines and curves (Figure 12a). Next, a circle was extruded along every curve, thereby resulting in a cerebral arterial system made up of tubes (Figure 12b); and these tubes were tweaked in a way, that their ends are narrowed and closed (Figure 12c).
Image showing the traced cerebral arteries using the CV curve tool in the three different orthographic views namely, X-axis (bottom right), Y-axis (top left), and Z-axis (bottom left). The top right block shows us the default perspective view.
(a) Image showing the cerebral arterial system made up of lines and curves. (b) Image showing the cerebral arterial system made up of tubes. (c) Image showing the cerebral arterial system with narrowed and closed ends. (d) Image showing the cerebral arterial system with approximated artery colour given from default colour palette.
The other minor appendages and extensions of the circle of Willis were drawn on a plane, followed by deletion of the unnecessary ones and finally the face of the model was extruded. Extrusion is mainly done to provide thickness, so that the thin line will transform into a vessel of appropriate thickness. The face extruded model was then applied to the retopologize function to clean up and smoothen the model. Finally, the circle of Willis was merged with its appendages through edge bridging and offset correction, resulting in the creation of the ‘cerebral arterial circulation system’ structure.
Similarly, the cerebral venous system, cranial nerves, cerebrum, cerebellum, brain stem (Figure 3) and the eyeball with TrueColor confocal images can be created.
The constructed model was given an approximated artery colour from the default colour palette (Figure 12d). This step can be done in Maya LT software or Blender software [21]. If Blender software is used, the 3D models have to be first exported from Maya LT software and imported into Blender software.
The 3D models can be successfully launched in AR after UV unwrapping and lighting, followed by coding the models for the AR module in Unreal Engine software for a successful run.
The 3D models have to be exported from Maya LT software and imported into Blender software for UV unwrapping. UV unwrapping is the process of cutting out a 3D model and placing it on a 2D plane. UV unwrapping is done so that the model can be lit in the absence of scene lights, which is very essential for a successful AR module.
If there is no light in the AR scene, the 3D models inside the Unreal Engine software will appear black (Figure 13a). If we add light to the AR scene in the Unreal Engine software, the Android mobile phones will not be able to process it. But, processing the model by the mobile phone is of utmost importance, as the AR module innovated by us needs an Android mobile phone platform to operate. Hence, a lightmap has to be generated and applied to the 3D models to view the models correctly (Figure 13b), which cannot be done in Unreal Engine software. Hence, these lightmaps have to be generated in Blender software and then imported into the Unreal Engine.
(a) Image showing the cerebral arterial system is appearing as black due to the absence of lightmap. (b) Image showing the cerebral arterial system is appearing in normal colour due to presence of lightmap.
The Unreal Engine is an integrated development environment (IDE) used to develop applications for various platforms [22, 23, 24]. The AR application is one such application that was coded in the Unreal Engine software [25]. The 3D models were exported from Blender software after UV unwrapping and imported into the Unreal Engine level file for the initiation of AR. Finally, the app (Eye MG AR) is built from the Unreal Engine for Android devices. The link for the app is given below:
A dataset array is set up in Unreal Engine software which contains the image of the AR template (Figure 4). When the program starts running, all the images in the camera view will be tracked. If any of the tracked images match with the AR template from the data set array, the 3D models will be spawned, with transform values matching the centre of the AR template. If the 3D model is already spawned, then the transform value is updated to the centre of the AR template and will go to the next frame. This is the algorithm for the AR module (Figure 14), and it is made to run on a loop at multiple frames per second (FPS) depending on the device.
Image showing the coding/algorithm of the AR module.
The 3D printing of ophthalmology related models has been proposed first by Ramesh et al. for enhancing learning through the concept of puzzle assembly (Figures 7-9) [26]. The concept of puzzle assembly can serve as a comprehensive self-learning tactile tool kit for neophytes [26, 27, 28, 29, 30, 31]. 3D printing models can overcome the limitations of the theoretical framework of textbooks used for studying [32, 33, 34, 35]. Practical sessions facilitate teaching and 3D printing anatomical puzzle models perfectly augment it cost-effectively.
The software used to create the 3D models was Maya LT. Cura software was used for printing the models in sliced layers. Cura software gives the output in an STL format, which is the standard tessellation language format for 3D printing FabX XL printer was used to print the Circle of Willis model and the eye. FabX Plus printer was used to print cerebral venous system model. Polylactic acid (PLA) material which is a biodegradable plastic, manufactured from corn starch, cassava and sugar cane waste was used for 3D printing all anatomical structures except the retina. For the retina, thermoplastic polyurethane (TPU) material was used for 3D printing.
The 3D models created by us are currently available for free download from the website (mcmi.in).
The PLA plastic costs approximately 13.43 USD for 1 kg weight. TPU costs approximately 40.28 USD for 1 kg weight.
The economics involved in 3D printing models is as follows:
Circle of Willis model costs approximately 6.71 USD for 400 g sample
Cerebral venous system model costs approximately 6.71 USD for 400 g sample
Eyeball model costs approximately 26.85 USD for 1 kg sample
The duration of printing the 3D models is as follows:
10 hours to print: The circle of Willis
5 hours to print: The cerebral venous system
48 hours to print: The eyeball
Cerebral arterial circulation and other allied anatomical structures are best understood with sound knowledge of their complex anatomy. In this chapter, we have simplified the anatomical learning of these complex anatomical structures with 3D AR models (in the free Android app Eye MG AR) and 3D printed models for better concept learning. This cognitive learning module of the cerebral circulation will aid in concept building for neophyte ophthalmologists, neurosurgeons, intensivists, physicians, and paramedics thus aiding in faster diagnosis, speedy treatment and effective rehabilitation.
We are grateful to Mr. Pragash Michael Raj (Department of Multimedia), and Mrs. Priyadharshini of Mahathma Eye Hospital Private Limited, Trichy, Tamil Nadu, India for their technical support throughout the making of this chapter and its illustrations. We sincerely express our thanks to Ms. Banasmita Mohanty for her support for the proofreading of this chapter. We are also grateful to Dr. Sabin Malik for his support and help with references for the anatomy of the cerebral models used for animation in this chapter.
The authors declare no conflict of interest.
I (Dr. Prasanna Venkatesh Ramesh) owe a deep sense of gratitude to my daughters (Pranu and Hasanna) and family (in-laws) for all their prayers, support, and encouragement. Above all, I extend my heartfelt gratitude to all the patients who consented to the images which are utilized for this chapter.
I (Dr. Shruthy Vaishali Ramesh) want to thank my partner (Arul) for his constant support and encouragement during the process of creating this chapter.
In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the chapter. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
3D models were created and used in animations by us in this chapter. This includes the human eyeball with TrueColor confocal fundus image, cranial nervous system, the cerebral venous system, cerebral arterial system (comprising of the circle of Willis), brain stem nuclei, extraocular muscle, meninges etc. These models help in better understanding and can be used in various fields of medicine. We have created models which are related to ophthalmology, which allows us to explain a disease or a condition with its pathophysiology, pathway, clinical features, tests, treatment and prognosis.
These models can be 3D printed, used for augmented reality simulations, used for virtual reality and can also be used for advanced mixed reality with Microsoft HoloLens. 3D models when used for real-time teaching, especially with the help of multimodal fundus images, microscopic structures like the trabecular meshwork, angles, diseases of lens etc., can pave the way for new-age pedagogy. We have created apps using these models like the Eye MG AR (https://play.google.com/store/apps/details?id=com.EyeMG_AR) and Eye MG 3D (https://play.google.com/store/apps/details?id=com.EyeMG_3D) which are based on augmented reality model of the eye and multimodal fundus imaging atlas, respectively. These are available for Android users and are free to download from Google Play Store. An app for iPhone users, named Eye MG Max is currently available in App Store. In this application, eyeball with TrueColor confocal fundus images, and all structures related to ophthalmology are provided with a user-friendly interface. In Eye MG Max, multiple views with transparency for viewing the structures passing through another model, free camera mode, annotated modes, customised zoomed views and videos related to any ophthalmic pathology are provided; thus, providing a 3D atlas at the user’s fingertip for comprehensive learning.
three-dimensional anterior cerebral artery anterior communicating artery anterior inferior cerebral artery basilar artery cranial nerve external carotid artery frames per second internal carotid artery integrated development environment lateral geniculate body medial cerebral artery medial longitudinal fasciculus posterior cerebral artery posterior communicating artery posterior inferior cerebellar artery polylactic acid paramedian pontine reticular formation thermoplastic polyurethane vertebral artery
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The existence of relationships between environmental changes and health in humans and animal species is well known and it has become generally accepted that poor health affects the animal’s natural behaviors and animal welfare and, consequently, food safety and animal production quality. Microclimate alterations, husbandry-management conditions, quality of human-animal interactions, feeding systems, and rearing environment represent the main factors that could negatively affect animal welfare and may produce behavioral, biochemical, endocrine, and pathological modifications in domestic and wild animals. Particularly, high stress levels can reduce the immune system response and promote infectious diseases. Adverse socio-environmental factors can represent a major stimulus to the development of different pathologies. 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During March 2017, the Food and Agricultural Organization of the UN through its ‘Rome Declaration’ called for the urgent need to combat RPW by collaborative efforts and commitments at the country, regional and global levels to stop the spread of this devastating pest. There exist gaps and challenges in almost all the components of the current RPW-IPM strategy, particularly with regard to early detection, developing and implementing phytosanitary measures, lack of effective biological control agents in the field and poor farmer participation in the control programmes, which have made RPW control and eradication extremely difficult. This chapter gives an overview of the global invasion, current management options, challenges and future prospects for its effective control.",book:{id:"9698",slug:"invasive-species-introduction-pathways-economic-impact-and-possible-management-options",title:"Invasive Species",fullTitle:"Invasive Species - Introduction Pathways, Economic Impact, and Possible Management Options"},signatures:"Hamadttu Abdel Farag El-Shafie and Jose Romeno Faleiro",authors:[{id:"192142",title:"Dr.",name:"Hamadttu",middleName:null,surname:"El-Shafie",slug:"hamadttu-el-shafie",fullName:"Hamadttu El-Shafie"},{id:"320867",title:"Dr.",name:"Jose",middleName:null,surname:"Romeno Faleiro",slug:"jose-romeno-faleiro",fullName:"Jose Romeno Faleiro"}]},{id:"72961",title:"Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae): An Invasive Insect Pest Threatening the World Tomato Production",slug:"-em-tuta-absoluta-em-meyrick-lepidoptera-gelechiidae-an-invasive-insect-pest-threatening-the-world-t",totalDownloads:635,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"The South American tomato pinworm or tomato leaf miner (TLM), Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a serious invasive and destructive insect pest of tomato (Solanum lycopersicum L.) worldwide. The moth can cause 100% damage in tomato crop in both greenhouses and open fields if control measures are not carried out. Due to the high reproduction potential, dispersal ability, and tolerance to environmental conditions, the TLM invaded most tomato-producing countries in Europe, Africa, and Asia. The tomato leaf miner originated in South America and was first introduced in Spain in 2006 and from where it spread to other part of the world. 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