\r\n\t- Traditionally accepted topics related to global health security, \r\n\t- The impact of human activities and climate change on “planetary health”, \r\n\t- The impact of global demographic changes and the emergence chronic health conditions as international health security threats. \r\n\t- A theme dedicated to the COVID-19 Pandemic, \r\n\t- Novel considerations, including the impact of social media and more recent technological developments on international health security.
\r\n
\r\n\tThe goal of this book cycle is to provide a comprehensive compendium that will be able to stand on its own as an authoritative source of information on international health security.
",isbn:"978-1-78985-940-9",printIsbn:"978-1-78985-939-3",pdfIsbn:"978-1-83962-154-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"edbc267908c2f140f991de15d99276df",bookSignature:"Dr. Stanislaw P. Stawicki, Michael S. Firstenberg, Dr. Sagar C. Galwankar and Dr. Andrew C. Miller",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10624.jpg",keywords:"Threats, Monitoring, Food Security, Emerging Infections, Transmission, Geopolitics, Climate Change, Cyber Health Security, COVID-19, Novel Coronavirus, Pandemic, Coronavirus",numberOfDownloads:239,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 20th 2020",dateEndSecondStepPublish:"November 5th 2020",dateEndThirdStepPublish:"January 4th 2021",dateEndFourthStepPublish:"March 25th 2021",dateEndFifthStepPublish:"May 24th 2021",remainingDaysToSecondStep:"4 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"An Associate Professor of Surgery at Temple University School of Medicine and a Chair of the Department of Research and Innovation, St. Luke's University Health Network. A member of multiple editorial boards and co-author of over 550 publications.",coeditorOneBiosketch:"An Associate Professor of Surgery & Integrative Medicine at Northeast Ohio Medical University and Cardiothoracic Surgeon at the Summa Health Care System. A prolific writer and presenter, with multiple books, hundreds of peer-reviewed articles, and innumerable presentations around the world.",coeditorTwoBiosketch:"A CEO of the INDUSEM Health and Medicine Collaborative, Global Executive Director. of the American College of Academic International Medicine (ACAIM) and head of the World Academic Council of Emergency Medicine.",coeditorThreeBiosketch:"A Director of Research in the Department of Emergency Medicine at Nazareth Hospital in Philadelphia, USA, and co-chief editor of the International Journal of Critical Illness and Injury Science. A recipient of numerous local, regional, and national awards.",coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki",profilePictureURL:"https://mts.intechopen.com/storage/users/181694/images/system/181694.jpeg",biography:"Stanislaw P. Stawicki, MD, MBA, FACS, FAIM, is Chair of the Department of Research of Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania, and Professor of Surgery at Temple University School of Medicine. Dr. Stawicki has edited numerous books and book series on the topics of clinical research, medical education, medical leadership, patient safety, health security, and various other subjects. He is a member of multiple editorial boards and has co-authored more than 650 publications. He served as the inaugural president of the American College of Academic International Medicine (ACAIM) and directed its Taskforce on International Health Security. He has given a multitude of scientific presentations around the globe and is board certified in general surgery, surgical critical care and neurocritical care.",institutionString:"St. Luke's University Health Network",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"29",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"St. Luke's University Health Network",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:{id:"64343",title:null,name:"Michael",middleName:"S.",surname:"Firstenberg",slug:"michael-firstenberg",fullName:"Michael Firstenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/64343/images/system/64343.jpeg",biography:"Dr. Michael S. Firstenberg is a board-certified thoracic surgeon. He is the current Director of Research and Special Projects for the William Novick Global Cardiac Alliance. Previously, he was Chief of Cardiothoracic and Vascular Surgery at the Medical Center of Aurora and Rose Hospitals. He currently holds appointments in the Colleges of Medicine and Graduate Studies at Northeast Ohio Medical University. He attended Case Western Reserve University Medical School, received his General Surgery training at University Hospitals in Cleveland, and completed Fellowships at The Ohio State University (Thoracic Surgery) and The Cleveland Clinic (Surgical Heart Failure). He is an active member of the Society of Thoracic Surgeons (STS), American Association of Thoracic Surgeons (AATS), the American College of Cardiology (ACC), and the American College of Academic International Medicine (ACAIM – for which he is a Founding Fellow and President-elect). He also currently serves on several professional society committees. He is the author of well over 200 peer-reviewed manuscripts, abstracts, and book chapters. He has edited several textbooks on topics ranging from Medical Leadership, Patient Safety, Endocarditis, and Extra-corporeal Membrane Oxygenation – all of which include topics that he has lectured on world-wide.",institutionString:"William Novick Global Cardiac Alliance",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"22",totalChapterViews:"0",totalEditedBooks:"10",institution:null},coeditorTwo:{id:"293168",title:"Dr.",name:"Sagar C.",middleName:null,surname:"Galwankar",slug:"sagar-c.-galwankar",fullName:"Sagar C. Galwankar",profilePictureURL:"https://mts.intechopen.com/storage/users/293168/images/system/293168.jpeg",biography:"Sagar C. Galwankar, MBBS, DNB, MPH, FAAEM, FAIM, graduated from Pune University, India, as a MBBS Allopathic Physician in 1995. He is residency trained and board certified in internal medicine and emergency medicine in India and the United States, respectively. He is a prestigious fellow of the Royal College of Physicians, UK, and completed a MPH with additional training in Business Management in the United States. His academic experience over the last two decades includes consistent achievements and innovative strategies that have led to the creation of organizations, publication of landmark papers, and commendation with prestigious citations and honors for his works that have impacted academic medicine globally. He has played a defining role in founding and building internationally recognized interdisciplinary indexed journals. He is the CEO of the INDUSEM Health and Medicine Collaborative and heads the World Academic Council of Emergency Medicine (WACEM). Additionally, he serves as the Global Executive Director for the American College of Academic International Medicine (ACAIM). He is the Director for Research in Emergency Medicine at Florida State University (FSU) and serves as a core faculty for the FSU Emergency Medicine Residency Program, at Sarasota Memorial Hospital in Florida.",institutionString:"Florida State University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of South Florida",institutionURL:null,country:{name:"United States of America"}}},coeditorThree:{id:"317540",title:"Dr.",name:"Andrew",middleName:"C.",surname:"Miller",slug:"andrew-miller",fullName:"Andrew Miller",profilePictureURL:"https://mts.intechopen.com/storage/users/317540/images/system/317540.jpg",biography:"Andrew C. Miller, MD, FACEP. Dr. Miller is the Director of Research in the Department of Emergency Medicine at Nazareth Hospital in Philadelphia, USA. He is a graduate of St. Louis University (2000) and Southern Illinois University School of Medicine (2005). He completed residencies in Emergency Medicine and Internal Medicine at the State University of New York (SUNY) Downstate Medical Center (2010) where he served as Chief Resident for Research. He completed fellowships in Pulmonary Medicine at the University of Pittsburgh Medical Center (2013) and Critical Care Medicine at the National Institutes of Health (2014). He is active in the American College of Academic International Medicine, and is co-chief editor of the International Journal of Critical Illness and Injury Science. He has a track record of publishing original research in high-impact journals, and has been the recipient of numerous local, regional and national awards from groups including the American Medical Association (AMA), Society for Academic Emergency Medicine (SAEM), American Academy of Emergency Medicine (AAEM), Emergency Medicine Residents Association (EMRA), and the Accreditation Council for Graduate Medical Education (ACGME).",institutionString:"Nazareth Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Nazareth Hospital",institutionURL:null,country:{name:"United States of America"}}},coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:[{id:"74452",title:"Resilient Health System and Hospital Disaster Planning",slug:"resilient-health-system-and-hospital-disaster-planning",totalDownloads:47,totalCrossrefCites:0,authors:[null]},{id:"75488",title:"Management of Blood Supply and Blood Demand to Ensure International Health Security",slug:"management-of-blood-supply-and-blood-demand-to-ensure-international-health-security",totalDownloads:0,totalCrossrefCites:0,authors:[null]},{id:"75095",title:"COVID-19 Pandemic and Mental Health of Nurses: Impact on International Health Security",slug:"covid-19-pandemic-and-mental-health-of-nurses-impact-on-international-health-security",totalDownloads:11,totalCrossrefCites:0,authors:[null]},{id:"75171",title:"Improving International Health Security in Resource-Scarce Regions: Leveraging upon the Initial Success of Combating COVID-19 to Fight Emerging Health Threats",slug:"improving-international-health-security-in-resource-scarce-regions-leveraging-upon-the-initial-succe",totalDownloads:18,totalCrossrefCites:0,authors:[null]},{id:"73634",title:"Supply Chain Management and Restart of Economy in Post COVID-19",slug:"supply-chain-management-and-restart-of-economy-in-post-covid-19",totalDownloads:170,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"205697",firstName:"Kristina",lastName:"Kardum Cvitan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/205697/images/5186_n.jpg",email:"kristina.k@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6672",title:"Vignettes in Patient Safety",subtitle:"Volume 3",isOpenForSubmission:!1,hash:"2c8b1831a8cceea8be146cbfbd582b81",slug:"vignettes-in-patient-safety-volume-3",bookSignature:"Stanislaw P. Stawicki and Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/6672.jpg",editedByType:"Edited by",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editedByType:"Edited by",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7043",title:"Clinical Management of Shock",subtitle:"The Science and Art of Physiological Restoration",isOpenForSubmission:!1,hash:"0f79000187ae93618e2213631e00047c",slug:"clinical-management-of-shock-the-science-and-art-of-physiological-restoration",bookSignature:"Stanislaw P. Stawicki and Mamta Swaroop",coverURL:"https://cdn.intechopen.com/books/images_new/7043.jpg",editedByType:"Edited by",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7925",title:"Embolic Disease",subtitle:"Evolving Diagnostic and Management Approaches",isOpenForSubmission:!1,hash:"70a90d1a07cc875f7eda4641fbf32339",slug:"embolic-diseases-evolving-diagnostic-and-management-approaches",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg and Mamta Swaroop",coverURL:"https://cdn.intechopen.com/books/images_new/7925.jpg",editedByType:"Edited by",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8645",title:"Contemporary Topics in Graduate Medical Education",subtitle:null,isOpenForSubmission:!1,hash:"76d224ba3c158c43fda8141a61ababd6",slug:"contemporary-topics-in-graduate-medical-education",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, James P. Orlando and Thomas J. Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/8645.jpg",editedByType:"Edited by",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7447",title:"Vignettes in Patient Safety",subtitle:"Volume 4",isOpenForSubmission:!1,hash:"88d9ec0c55c5e7e973a35eafa413ded2",slug:"vignettes-in-patient-safety-volume-4",bookSignature:"Stanislaw P. Stawicki and Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/7447.jpg",editedByType:"Edited by",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"55341",title:"Performance Analysis of an Integrated Starter-Alternator- Booster for Hybrid Electric Vehicles",doi:"10.5772/intechopen.68861",slug:"performance-analysis-of-an-integrated-starter-alternator-booster-for-hybrid-electric-vehicles",body:'\n
1. Introduction
\n
As the electrification of vehicle propulsion at low (e-bikes) and high power (buses) continues to extend, the current research efforts on this topic are focused especially on increasing the autonomy of vehicles due to the accumulation of electricity. Due to the lack of charging station and low autonomy in terms of maintaining a reduced weight of the battery, the electrical vehicle is momently limited to urban trails. In this context, the hybrid electric vehicles (HEVs) were considered initially as a transition between conventional vehicles (internal combustion engine (ICE)) and the electric ones, and now they still remain a viable solution that is gaining ground by combining the advantages of both types of vehicles [1–4].
\n
The trend in all types of vehicles (conventional, electrical, or hybrid vehicles) for the next years is to increase the equipment with different types of electrical subsystems. These can be related to the safety (direction, breaking, lights, distance sensors, mirrors etc.) or to the comfort (seats, HAVC, audio, navigation display etc.). At the same time, a lot of traditional mechanically driven loads are replaced with electrical driven ones (water pumps, servo steering, ventilation fan, etc.). This demand of electrical energy, of around 10 kW [5], requires increasing generator power and a certain level of efficiency (normally situated at 40–55%) [6]. A common alternator in a car is relatively cheap and with low efficiency, but with the expected increase of power, it exceeds the capability of the Lundell generator (claw pole synchronous machine). In this context, the replacement of classical alternator with a high efficiency machine is mandatory. Besides this, the operating mode of the conventional starter (around 1 s for each start) is used only for the start of the ICE and after it becomes an extra weight in the vehicle. The easy (costs and implementation) solution of this problem is to replace both machines (starter and alternator) with a single electrical machine.
\n
The initial concept of the integrated starter-alternator (ISA) system was developed in order to gain more space for the powertrain system and to reduce the weight of the vehicle by combining the starter with the alternator. This system ensures the start/stop of the internal combustion engine and the supply with electricity of all the auxiliary subsystems (safety or comfort).
\n
Especially in parallel configuration of HEV, the ISA is used for starting the internal combustion and supply the electrical load. A second electrical machine is necessary for the electric propulsion. The method for the simplification of this structure involves the use of a single electric machine comprising three operating modes: starter-alternator and booster. In this case, the integrated starter-alternator-booster (ISAB) system will be able initially to start the ICE, then, when it is turned on, it will reverse to generator mode and will supply electricity to consumers and the storage system. By adopting adequate control strategies, the electrical machine is capable of moving quickly from generator to motor (booster) and back in order to help the international combustion engine for a short period of time (maximum 2–3 min), if more power is necessary (overruns, ramp, curbs, etc.) [7]. This operating mode of the machine is generically called integrated starter-alternator-booster (ISAB). Using ISAB in parallel HEV is generically called Mild-HEV. In this configuration, the full electric propulsion of the vehicle is not possible, but the production costs necessary for the implementation of the hybridization in conventional vehicles are lowest compared to other variants of HEV.
\n
According to Ref. [8], where the influence of fuel consumption for a small car equipped with ISAB is investigated and considering the European standard (1999/100 EC), the fuel consumption is reduced to about 12% in total.
\n
The increase in the number of electric components within the vehicles boosts the market for electrical motors for hybrid and electric vehicles. A Frost & Sullivan market research finds that the market earned revenues of about 55 million Euros in 2010, which are expected to reach $1.6 billion by the end of 2017 [9].
\n
The required characteristics of the ISAB in the starter mode and alternator (generator) mode are very restrictive for a conventional electrical machine [10]:
\n
High value of electromagnetic torque for starting ICE (120–300 Nm).
High efficiency at wide speed range (600–6000 rpm).
Reliability at high vibrations and over 250,000 start/stop cycles (during 10 years).
Operation at temperatures between −30 and 130°C.
Easy maintenance and low cost and so on.
\n
Usually, the ISAB can be connected with a gasoline or diesel engine, either directly through the crankshaft (see Figure 1) or indirectly through the belt system (see Figure 2); based on that, the systems are called belt-driven starter-alternator-booster (BSAB) and conventional ISAB, respectively.
\n
Figure 1.
The ISAB system.
\n
Figure 2.
The BSAB system.
\n
The size of the electrical machine is very important for BSAB application in order to keep the overall size low (the same dimensions like the ones of a conventional alternator) but for a given maximum torque, the systems usually have a recommended gear ratio 3:1 to the ICE crankshaft, according to Ref. [8]. The BSAB runs with a speed three times higher than the ICE. For the ISAB, the speed range is usually synchronized with combustion engine.
\n
\n
2. Electrical drive used for ISAB applications
\n
2.1. Electrical machines
\n
In the last decade, the development of power electronics (inverter/convertor) made the alternative current (AC) machines the best solution for ISAB applications, especially due to their high power density. These are synchronous reluctance machine (SynRM), induction machine and permanent magnet synchronous machines (PMSM) in both supplying variants: with sinusoidal and trapezoidal current.
\n
The detailed investigation of SRM and induction machine is presented in Refs. [11, 12]. In these studies, the complicated electronics needed for SRM and the difficult control of the induction machine (influence of slip in performance of the machine) are highlighted. In this context, the SynRM and PMSM are the best candidates for ISAB applications.
\n
The electrical machines used for conventional ISAB applications are exposed at high temperatures generated by ICE. This makes impossible the use of the PMSM in high efficiency and low-cost conditions (only with a special method for cooling or using expensive SmCo magnet). Therefore, the SynRM without permanent magnets is the best solution for the direct connection to the crankshaft of ICE (ISAB) and PMSM machine for BSAB.
\n
2.1.1. PMSM machine for BSAB applications
\n
The main advantage of the PMSM compared with other types of electrical machine is their high efficiency due to the absence of the field coil losses. The stator is constructed from three-phase windings and steel sheets (the same as the induction machine), but due to the absence of iron losses, the rotor is built from massive steel and permanent magnets. The position of the permanent magnets can be categorized as surface-mounted type and interior type. This position can have a significant effect on the mechanical and electrical characteristics, especially on the synchronous inductance [13]. Because the permeability value of rare earth magnet (such as NdFeB) is very close to that of the air, the air gap of the machine with mounted surface PM effectively becomes larger in this case. This makes the machine d-axis inductance value very low, with a significant effect on the ability of overloading the machine and operation at flux weakening. Because the maximum torque is inverse proportional with the d-inductance, this becomes very large. But the low value of d-inductance reduces the possibility to operate at flux weakening. This is caused by the need to use a high value of the demagnetization component of the stator current in order to decrease the flux value in the air gap. Therefore, the remained current on the q axis will be insufficient to produce torque.
\n
In the case of the interior magnets, it is possible to obtain a sinusoidal distribution of the air-gap flux by using simple rectangular magnets. A sinusoidal flux distribution reduces considerably the cogging torque, in particular in the case of the machine with a large number of pole pairs and a small number of slots per pole and phase [14]. For these structures, it is also possible to increase the flux density in the air gap beyond the value of the remnant flux density of the magnets by using the flux concentrators. Because in this case the d-inductance is usually higher than with that of the surface magnets topologies, the overload capacity of the machine will be reduced and the performance in flux weakening conditions will be higher.
\n
The PMSM with outer rotor (PMSMOR) (see Figure 3) is one of the special topologies of PMSM, with some advantages for BSAB applications:
\n
Belt mounted directly on the outer rotor, without using pulley.
Easy mounting of permanent magnets, the centrifugal forces do not influence their mechanical stability.
High torque capabilities.
Convenience of cooling, etc.
\n
Figure 3.
PMSMOR type.
\n
The development cycle of PMSM (inner or outer rotor) topologies includes analytical procedure, magnetic field analysis and optimization procedure connected to previous design steps. The analytical procedure is presented in detail in Refs. [13, 14] and includes the following topics: analysis of the specifications, selection of the topology, the active and passive materials, sizing the machine, choice of the manufacturing technologies and information about preliminary cost evaluation. In the dimensioning procedure, classical formulas or dedicated software platforms like SPEED software can be used.
\n
The electromagnetic flux analysis is realized with dedicated programs (like Flux 2D/3D, Jmag 2D/3D, Maxwell 2D/3D, ANSYS, Opera, open-source programs, etc.) based on the finite element method (FEM). The FEM is a widely used method for obtaining a numerical approximate solution for a given mathematical model of the machine. The obtained results are related to the voltage/current waveform, map of flux density, electromagnetic torque, losses (iron and Joule), and the efficiency value or map of it.
\n
The optimization of electric machine is a multivariable, nonlinear problem with constraints. In order to treat problems with constraints, it is necessary to transform them into unconstrained ones. This can be done, for instance, by embedding the constraints in the objective function. The most used optimization algorithms in design of all types of electrical machines are as follows: genetics algorithms (GA), differential evolution algorithm (DEA), estimation of distribution algorithms (EDAs), particle swarm optimization (PSO) and multi-objective genetic algorithms (MOGA, Pareto, etc.) [15].
\n
A comprehensive evaluation of optimization algorithms was performed in Refs. [16–18]. The authors of these studies state that any such classification of different optimization algorithms is not truly appropriate since the performance is an objective closely related to the specifics of each application. Nevertheless, in the optimization of the electrical machine, the authors mostly agree that DEA achieves the best fitness values, i.e. the minimum objective function value, usually with a smaller number of evaluation steps.
\n
Considering the important step in the development of cycle of PMSM presented above, a general design procedure of PMSMOR for BSAB applications is proposed and presented in Figure 4.
\n
Figure 4.
General design procedure of PMSMOR.
\n
\n
2.1.2. SynRM machine for ISAB applications
\n
Variable reluctance synchronous machines have received little attention in various comparative studies approaching the selection of the most appropriate electric-propulsion system for either HEV or EV. Malan [19, 20] showed that the SynRM drive has major advantages in electrical propulsion. SynRM’s performance strongly depends on the saliency ratio, but increasing the saliency complicates the rotor construction and drastically increases the motor cost. Interesting results concerning the influence of the saliency ratio on the SynRM steady-state performances, mainly on power factor and efficiency, are given in Ref. [21], while the effect of rotor dimensions on d- and q-axis inductances in the case of a SynRM with flux barrier rotor is discussed in Ref. [22]. Thus, the number of rotor flux barrier for the SynRM recommended in the literature is four. Above this value, the technology of the rotor is too complicated, while for a value lower than 4, the value of the torque ripple is too high. Regarding the rotor construction, there are three main different types, given in Ref. [23], presented in Figure 5.
\n
Figure 5.
Rotor topologies for a SynRM: (a) simple salient pole, (b) axially laminated anisotropy rotor, and (c) transversally laminated anisotropic rotor. Source: [23].
\n
With salient rotor poles (see Figure 5a): require low technological effort and are obtained by removing the iron material from each rotor pole in the transversal region.
With axially laminated rotor (ALA) (see Figure 5b): the rotor core is made of axial steel sheets that are insulated from each other using electrically and magnetically insulation (passive material).
Transversally laminated anisotropic rotor (TLA) (see Figure 5c): the so-called ribs are obtained by punching and then the various rotor segments are connected to each other by these ribs.
\n
The SynRM has a larger torque density compared with that of IM. This comes from the absence of rotor cage and related losses. A different dynamic behaviour is expected from SynRM due to the specific relationships between currents and fluxes. Because SynRM does not have a traditional cage (especially used for starting), it is necessary to use the modern inverter technology. Therefore, most of the literature on SynRM drives has concentrated mainly on the design and control of the machine with the goal of improving control, efficiency and torque production, drive flexibility and cost [24].
\n
The main drawback of SynRM is related to structural behaviour at high speeds (over 10,000 rpm) because the specific geometry of the rotor involves thin layers of steel and large cut-off areas.
\n
Based on advantages and disadvantages of the SynRM and the specific applications of ISAB (rated speed up to 10,000 rpm), SynRM is one of the most suitable candidates for direct connection to crankshaft. The major advantages are high torque, thermal behaviour (absence of permanent magnets and low average value of iron losses), high value of efficiency at entire drive cycle of functioning, vibro-acoustic behaviour (low noise), etc.
\n
In the development cycle of SynRM presented below, the most important step is related to the rotor geometry and the structural behaviour (see Figure 6).
\n
Figure 6.
General design procedure of SynRM.
\n
\n
\n
2.2. Power electronics
\n
The electrical equipment installed on the vehicles operates at a nominal voltage of 14 V. In the early 1990s, a new standard (PowerNET) for automotive electrical systems has been proposed by a consortium of automotive manufacturers (Daimler-Benz and General Motors). Following a proposal by the PowerNET, the voltage level increases for the electrical installation to 42 V [25]. The goal was to reduce the section of the conductors and gain the possibility to increase the total power installed in the new generation of vehicle. The standard did not become very popular because of its high implementation costs, which would require the redesign of all electrical and electronical subsystems [26]. Instead, most producers were oriented on systems with two voltage levels: high voltage for propulsion and low voltage for auxiliary and electronic subsystems.
\n
A starter-alternator system involves the use of a static frequency converter for the driving of the electrical machine. The convertor will operate in both the inverter and rectifier regimes. In the rectifier operating mode, it is indicated to adopt a control strategy of the converter with the purpose of reducing losses and the harmonic content of the output currents of the machine. The techniques for the control of the converter for these two modes are the same, only the current reverses its sense depending on the operating mode.
\n
The input voltage of the static frequency converter is a DC voltage, the value of which must be kept constant in order to function optimally. The regulation of the input voltage of the converter can be done by using a bidirectional DC/DC converter with a closed loop control. An alternative to the use a DC/DC stage converter and another DC/AC converter is to use a Z-Source Converter [27]. The Z-Source Converter is more capable compared with the classical converter to operate both as a boost and buck converter due to the input impedances that give it particular operating properties.
\n
2.2.1. Power electronics of SynRM and PMSM
\n
For the control of PMSM machine, the current of the q axis is maintained maximum in order to produce high value of the torque and zero for d axis current, respectively. Instead, for SynRM, the control strategies mean to keep the equal value of the q axis current with the d axis. In the case of PMSM with interior magnets, this control strategy does not provide maximum torque due to the additional reluctant torque [28] component that appears in expression:
\n
T=32⋅p⋅[ΨPM⋅iq−(Lq−Ld)⋅id⋅iq]E1
\n
where T is the electromagnetic torque, p is a pair pole number, ΨPM is the permanent magnet flux, iq is q axis current, id is d axis current, and Lq, Ld are q axis and d axis inductances.
\n
The reluctant component of the torque has a maximum value for id ≠ 0 and the stator current equal with π/4.
\n
Usually, the implemented control method for the PMSM and SynRM for automotive application is an indirect method, which is based on measuring the stator currents and calculating the rotor flux phasor magnitude and position using these currents and the rotor position. Thus, the flux transducer or flux estimators that are usually used in the vector control method with direct measurement of flux are eliminated. This method has a disadvantage due to the fact that the accurate determination of rotor flux phasor position requires a precise measurement of rotor position. Thus, the practical implementation using speed measurement for obtaining the integration of the rotor angle is not recommended. Hence, an incremental encoder position or a resolver, which has a higher cost while providing the precision required of a vector control with a good dynamic response in applications is used. In addition to this vector control method that uses position sensors for determining the rotor angle control, other methods where these transducers are eliminated (sensorless) exist. In these cases, the rotor position is estimated by using complex algorithms, using as input the measurement values of voltages and currents [29].
\n
The general diagram control presented in Figure 7, usually used for PMSM and SynRM, can be divided into power and control components. The power circuit consists of the electrical machine (PMSM/SynRM), DC/DC converter, inverter, while the control loop consists of speed transducer, current transducers, PWM signal generation block, transformation of coordinate systems blocks and computing block of references current.
\n
Figure 7.
Block diagram of vector control system for PMSM and SynRM.
\n
The control strategies considered for the SynRM are:
\n
Maximum torque control per ampere control (MPTAC)
The model of control is based on imposing the same currents for the d and q axes of the machine as current references for the vector control of the machine. These currents are calculated from the torque equation like
id=iq=Trefp⋅(Ld−Lq)E2
Maximum rate of change of torque control (MRCTC)
The control strategy is implemented in order to obtain fast machine response at sudden torque steps of the load. The idea here is to compute the d and q current component functions of some machine parameters and to use these components as input of the vector control scheme. The detailed control strategy is presented in Ref. [30].
Maximum power factor control (MPFC)
The aim of this method is to maximize the power factor of the machine. For this, the d and q current components are computed as follows:
Iqimposed=Tref⋅1p⋅1Ld−Lq⋅1Id(from the machine)E3
\n
Idimposed=Iqimposed⋅cos(θ)sin(θ)E4
\n
For the ideal machine, θ is in the range 0–90° and gives best performance at 45°. For a real machine, it has to be computed by varying its value and observing the performance of the machine for each angle step.
\n
\n
\n
\n
3. Simulation of a hybrid electric vehicle with the ISAB system
\n
In order to study the electrical machines in ISAB applications, the electric drive model can be introduced and simulated in the Advanced Modelling Environment for performing Simulation (AMESim). AMESim is a multi-domain simulation software for the modelling and analysis of one-dimensional (1D) systems. In this program, each component or physical phenomenon is described by differential equations, type formulation in which the major variable is the time [31]. This approach is different from the partial derivate equations formulation, which formalizes the notion of the distribution of system properties in space. The representation of a dynamic system starting from the notion of “multiport” consists of highlighting the energy exchanges between a component and its environment through the connecting ports. The connection of two or more components through the port allows port exchange power (electrical, mechanical, etc.) according to the adopted sign convention.
\n
For automotive applications, the program comprises discrete components of the ICE, gearbox, control system, electric loads, electrical machine and power inverter, connected together to form a global model of a hybrid electric vehicle.
\n
The geometrical and electrical parameters of electrical machine considered for ISAB (SynRM) and BSAB (PMSMOR) application are presented in Table 1. The configuration of PMSMOR is a three-phase machine with 36 slots and 15 poles, and the SynRM topology is a three-phase machine with 27 slots and 4 poles. The dimension of PMSMOR has been imposed according to Ref. [32] (data chosen for belt brushless alternator).
\n
Parameter
PMSMOR
SynRM
Output power (W)
6500
10,000
Rated speed (rpm)
400
800
Phase voltage (V)
72
100
Number of phases (–)
3
3
Number of pole pairs (–)
15
2
Number of slots
39
30
Stator outer diameter (mm)
176
260
Stack length (mm)
150
150
Rotor outer diameter (mm)
210
210
Tooth width (mm)
5
6
Permanent magnet height (mm)
8
–
Residual flux density—NdFeB-N48 (T)
1.4
–
Coercive force—NdFeB-N48 (kA/m)
796
–
Stator and rotor (only for SynRM) lamination type
M270-35A
Rated current (A)
72
72
Current density (A/mm2)
7
6
Iron losses (W)
212
623
Torque (N m)
150
150
Power factor
0.9
0.85
Efficiency (%)
90
87
Saliency ratio
–
4.1
Table 1.
Geometrical and electrical parameters of PMSMOR and SynRM.
\n
The simulation of the BSAB and ISAB is carried out on a New European Driving Cycle (NEDC). A driving cycle is a series of points defining a speed profile that the studied vehicle must follow [33]. The defined speed profile simulates most common operating modes of an automobile (frequent acceleration and deceleration, load variations and speed variations) and corresponds to both urban and extra-urban environments. The parameters and the profile of NEDC are presented in Table 2 and Figure 8, respectively.
\n
Time (s)
Distance (km)
Max speed (km/h)
Average speed (km/h)
Max acceleration (m/s2)
Max deceleration (m/s2)
Idle functioning (s)
Stops
1184
10.93
120
33.21
1.06
-1.39
298
12
Table 2.
NEDC parameters.
\n
Figure 8.
NEDC profile.
\n
The model takes into account the most complex thermodynamic phenomena occurring in a heat engine. In the initial implementation, the starter and alternator were a DC permanent magnets machine and the Lundell generator, respectively. The model has been replaced by the studied model and is shown earlier (PMSMOR/SynR). The motors are powered from a battery through the converter DC/DC that will operate in this case as a boost converter.
\n
The evaluation of the performance of PMSMOR and SynRM was started from a demonstration model in AMESim of a compact car category (see Figures 9 and 10) with a compression-ignition combustion engine. The imposed weight of the vehicle was 1200 kg (usually between 1134 and 1360 kg, according to Ref. [34]) without any extra weight or passengers.
\n
Figure 9.
Structural diagram of the vehicle.
\n
Figure 10.
Vehicle model [35].
\n
In order to have comparative results regarding the fuel consumption, in the first simulation, the conventional vehicle functioning during the NEDC cycle was tested. In the next simulations, the ISAB regime with considered electrical machines was established. The behaviour of the starter and alternator in the vehicle model was supposed to be the same as in a conventional car. For the booster regime, a set-up to help ICE for 15 min/h was added and this works in the booster regime only when the battery was fully charged (up to 95%). The time limit for each booster regime was set at 2 min in order to avoid the complete discharging of the battery (but no less than 20%). The parameters of the ICE considered are presented in Table 3.
\n
Type
Turbo diesel
Compression ratio
2:1
Number of cylinders
4
Maximum torque
365 N m at 2000 rpm
Cubic capacity
1994 cm3
Maximum power
120 kW at 3750 rpm
Table 3.
ICE parameters.
\n
The control of the electrical machines in the starter operating mode involves a maximum torque value (150 N m) until the ICE reaches 350 rpm. Torque command is provided by a bi-positional regulator with hysteresis. It is active when the command of ICE is active and its speed is less than 200 rpm, and it is off when the speed exceeds 400 rpm. When the ICE speed exceeds 300 rpm, the process of fuel injection into the cylinders starts and the ICE accelerates to idle speed. By applying the necessary torque to start the ICE, this is accelerated rapidly at the speed of 400 rpm in about 0.35 s.
\n
When ICE exceeds the speed of 400 rpm, the bi-positional controller becomes inactive and the combustion engine continues to spin out due to its inertia. If the pistons do not reach the maximum compression point, they will not be able to inject fuel to start the combustion process; consequently, the speed drops below 200 rpm and now the controller output is active. Therefore, the starter is controlled again and the combustion engine is brought to a speed of 400 rpm. At the start of the combustion engine process, ICE is accelerated to the idle speed, where it is maintained by the electronic control unit. The entire process of starting the engine (in normal condition), from the beginning until stable operation at idle speed, lasts 0.8 s. In the winter, this process may take 1.5 s. The speed profile of starting the ICE is presented in Figure 11.
\n
Figure 11.
Speed profile at starting ICE.
\n
For the alternator mode, the nominal value of the electrical loads is considered in the model. Some electrical loads are intermittently connected (fan, electrical window, heating systems, etc.). Other loads are dependent on ICE speed (fuel pump and injectors) or the speed of the vehicle.
\n
When the entire driving cycle is considered, the fuel consumption in the vehicle is reduced to 878.63 ml for the BSAB system and 941 ml for the ISAB system. These values represent a fuel economy of around 16% for BSAB and 17.3% for ISAB of total consumption compared with a classical vehicle with a dedicated alternator and starter (without booster option) system. The difference in fuel consumption is due to the value of nominal power of electrical machines (see Table 1). But, the performances of SynRM are limited by the battery (which uses 75 Ah) capacities. If it uses a stronger battery, the total fuel economy can be increased with 2 or 4% (especially due to the booster mode).
\n
In the mechanical evaluation of electrical machines for automotive applications, the variation of electromagnetic torque is one of the most important parameters, because this variation (torque ripple) can become a source of noise and vibration in vehicles. Thus, for a better visualization of the torque profile of PMSMOR and SynRM, a new scenario for all three regimes was considered. For better comparative results (variation of axis torque) between IASB and BSAB, the BSAB system is taken into account through directly coupling (using ratio 1:1 between ICE and BSAB speed) at ICE. The starter and generator regime has been set for 1.5 and 20 s, respectively. The variation of the axis torque in the generator mode has been obtained by intermittent connection of the electrical loads (lights, HVAC, media, etc.). For the booster mode, the speed of the vehicle is increased from 70 to 120 km/h in 17 s, necessary to overtake other vehicles. In this case, the battery is considered fully charged.
\n
Figures 12 and 13 show the variation of the axis torque versus time for all operating modes, respectively. Due to the proper windings-slot combination, the torque ripple values are below 10%. In fact, the ratio of the torque ripple is 7.1% for PMSMOR and 6.2% for SynRM. In the booster mode, the rated torque value of the 10 kW SynRM machine used for ISAB is obviously bigger than that of the 6.5 kW PMSMOR.
\n
Figure 12.
BSAB torque profile.
\n
Figure 13.
ISAB torque profile.
\n
\n
4. Conclusions
\n
The chapter presents the main steps to be followed in the development of a specific electric drive system dedicated to automotive domain, such as integrated starter-alternator-booster applications. Replacing the starter and alternator in a conventional vehicle with extended possibility to work in booster mode represents the first step of vehicles’ hybridization, called Mild-HEV. In this way, two variants in mounting the ISAB had been identified in the literature: one, directly driven generic called ISAB and another belt-driven called BSAB. In this chapter, the approach contains the major elements that need to be discussed for two type of electrical machine (PMSMOR and SynRM) suitable for BSAB and ISAB, respectively. The general design procedure is presented for these two electrical machines by taking into account the typical constraints of the applications and the behaviour of the machine (thermal, structural, and noise, vibrations and harshness particularities). Also, the control aspects of both electrical machines are presented.
\n
In order to demonstrate the capability of this vehicle hybridization method, two electrical machines have been designed and the equations model was developed and implemented in the general 1D model of conventional vehicle performed in AMESim software. The influence of fuel consumption on the entire drive cycling (NEDC) was investigated. Based on the obtained results, the ISAB system gives a greater value of the reduction of fuel consumption, but the coupling of the electrical machine directly to the crankshaft involves complicated manufacturing techniques (higher cost) compared with the BSAB system procedure.
\n
Acknowledgments
\n
This work was supported by a grant of Strengthening the Research potential of CAREESD in the field of Electromechanical Systems and Power Electronics for Sustainable Applications, ESPESA, 692224/2015 H2020 TWINNing-2015 and ALNEMAD (PCCA 181/2012).
\n
\n',keywords:"electrification, hybrid electric vehicle, integrated starter-alternator-booster, electrical machine",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/55341.pdf",chapterXML:"https://mts.intechopen.com/source/xml/55341.xml",downloadPdfUrl:"/chapter/pdf-download/55341",previewPdfUrl:"/chapter/pdf-preview/55341",totalDownloads:1505,totalViews:547,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,dateSubmitted:"October 26th 2016",dateReviewed:"March 28th 2017",datePrePublished:null,datePublished:"June 21st 2017",dateFinished:null,readingETA:"0",abstract:"The chapter aims to investigate the reduction of the fuel consumption of conventional vehicles using mild-hybridization and considering the New European Driving Cycle (NEDC), using two topologies of electrical machines dedicated to integrated starter-alternator-booster (ISAB) applications: directly connected to the crankshaft (called ‘normal ISAB’) and indirectly through the belt system (called BSAB), respectively. The behaviour of ISAB and BSAB of a hybrid electric vehicle has been investigated with a multi-domain simulation software developed in Advanced Modelling Environment for performing Simulation (AMESim).",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/55341",risUrl:"/chapter/ris/55341",book:{slug:"hybrid-electric-vehicles"},signatures:"Florin-Nicolae Jurca and Mircea Ruba",authors:[{id:"180939",title:"Dr.",name:"Nicolae Florin",middleName:null,surname:"Jurca",fullName:"Nicolae Florin Jurca",slug:"nicolae-florin-jurca",email:"florin.jurca@emd.utcluj.ro",position:null,institution:{name:"Technical University of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"190371",title:"Dr.",name:"Mircea",middleName:null,surname:"Ruba",fullName:"Mircea Ruba",slug:"mircea-ruba",email:"mircea.ruba@emd.utcluj.ro",position:null,institution:{name:"Technical University of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Electrical drive used for ISAB applications",level:"1"},{id:"sec_2_2",title:"2.1. Electrical machines",level:"2"},{id:"sec_2_3",title:"2.1.1. PMSM machine for BSAB applications",level:"3"},{id:"sec_3_3",title:"2.1.2. SynRM machine for ISAB applications",level:"3"},{id:"sec_5_2",title:"2.2. Power electronics",level:"2"},{id:"sec_5_3",title:"2.2.1. Power electronics of SynRM and PMSM",level:"3"},{id:"sec_8",title:"3. Simulation of a hybrid electric vehicle with the ISAB system",level:"1"},{id:"sec_9",title:"4. Conclusions",level:"1"},{id:"sec_10",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Andreescu G-D, Coman CE. Integrated starter-alternator control system for automotive. In: Proceedings of the International Symposium on Computational Intelligence and Informatics (CINTI ‘13), 19-21 Nov. 2013, Budapest, Hungary, p. 339-343, Publisher: IEEE.'},{id:"B2",body:'Mirahki H, Moallem M, Rahimi SA. Design optimization of IPMSM for 42 V integrated starter alternator using lumped parameter model and genetic algorithms. IEEE Transactions on Magnetics. 2014, Vol: 5, NO: 3, pp. 1-6, DOI: 10.1109/TMAG.2013.2285358'},{id:"B3",body:'Rizoug N, Barbedette B, Sadoun R, Feld G, Starter-alternator propel the vehicle through a hybrid supply: Battery and supercapacitors. In: Proceedings of the Twenty-Seventh Annual IEEE Applied Power Electgronics Conference and Exposition (APEC’12); 5-8 February 2012; Orlando, Florida, USA. pp. 2583-2589, Publisher: IEEE.'},{id:"B4",body:'Mirahki H, Moallem M. Design improvement of Interior Permanent Magnet synchronous machine for Integrated Starter Alternator application. In: Proceedings of the International Electric Machines & Drives Conference (IEMDC’13); 12-15 May; Chicago, Illinois, USA. pp. 382-385, Publisher: IEEE.'},{id:"B5",body:'Parsa L, Goodarzi A, Toliyat HA. Five-phase interior permanent magnet motor for hybrid electric vehicle application. In: Proceedings of the IEEE Conference of Vehicle Power and Propulsion (VPPC’ 05); 7-9 September 2005; Chicago, Illinois, USA. pp. 631-637, Publisher: IEEE.'},{id:"B6",body:'Ivankovic R, Cros J, Kakhki MT, Martins CA, Viarouge P. Power electronic solutions to improve the performance of Lundell automotive alternators. In: Carmo J, editors. New Advances in Vehicular Technology and Automotive Engineering. Rijeka, InTech; 2012. DOI:10.5772/48459'},{id:"B7",body:'Jurca FN, Ruba M, Martis C. Analysis of permanent magnet synchronous machine for integrated starter-alternator-booster applications. In: Proceedings of the 2015 International Conference on Electrical Drives and Power Electronics (EDPE’15); 21-23 September 2015; High Tatras, Slovakia. pp. 272-276, Publisher: IEEE.'},{id:"B8",body:'Hagstedt D. Comparison of different electrical machines for belt driven alternator starters [thesis]. Lund: Department of Measurement Technology and Industrial Electrical Engineering, Lund University; 2013'},{id:"B9",body:'Frost & Sullivan, Strategic Analysis of Electric Motor Technologies for Electric and Hybrid Vehicles in Europe. http://www.automotive.frost.com [Accessed: 6-January 2017]'},{id:"B10",body:'Bae BH, Sul S.K, Practical design criteria of interior permanent magnet synchronous motor for 42V integrated starter-generator, In: Proceedings of the IEEE International Electric Machines and Drives Conference (IEMDC\' 03); 1-4 June 2003; Madison, Wisconsin, USA. pp. 656-662'},{id:"B11",body:'Schofield N, Long S, Generator operation of a switched reluctance Starter/Generator at extended speeds. IEEE Transactions on Vehicular Technology. 2009;58:48-56. DOI: 10.1109/TVT.2008.924981'},{id:"B12",body:'Rehman H. An integrated starter-alternator and low-cost high performance drive for vehicular applications. IEEE Transactions on Vehicular Technology. 2008;57:1454-1465. DOI: 10.1109/TVT.2007.909255'},{id:"B13",body:'Krishnan R. Permanent Magnet Synchronous and Brushless DC Motor Drives. Boca Raton, FL: CRC Press/Taylor & Francis; 2010. p. 611'},{id:"B14",body:'Gieras JF, Permanent Magnet Motor Technology: Design and Applications. 3rd ed. Boca Raton, FL: CRC Press/Taylor & Francis; 2011. p. 608'},{id:"B15",body:'Lei G, Zhu J, Guo Y. Multidisciplinary Design Optimization Methods for Electrical Machines and Drive System. Berlin/Heidelberg:/Springer-Verlag; 2016. p. 251'},{id:"B16",body:'Mutluer M, Bilgin O. Comparison of stochastic optimization methods for design optimization of permanent magnet synchronous motor. Neural Computing and Applications. 2012;21(8):2049-2056'},{id:"B17",body:'Deb A, Gupta B, Roy J. Performance comparison of differential evolution, genetic algorithm and particle swarm optimization in impedance matching of aperture coupled microstrip antennas. In: 11th Mediterranean Microwave Symposium (MMS); September 2011; Tunisia. pp. 17-20, Publisher: IEEE.'},{id:"B18",body:'Stipetic S, Miebach W, Zarko D. Optimization in design of electric machines: Methodology and workflow; In: Proceedings of the ACEMP-OPTIM-ELECTREMOTION join conference; 2-4 September 2015; Side, Turkey. pp. 1-8, Publisher: IEEE.'},{id:"B19",body:'Malan J, Kamper MJ. Performance of a hybrid electric vehicle using reluctance. IEEE Transaction on Industry Applications. 2001;37:1319-1324. DOI: 10.1109/28.952507'},{id:"B20",body:'Jurca FN, Ruba M, Martis C. Design and control of synchronous reluctances motors for electric traction vehicle. In: Proceedings of the 2016 International Symposium on Power Electronics, Electrical Drives, Automation and Motion (SPEDAM ’16); 22-24 June 2016; Anacapri, Italy. pp. 1144-1148, Publisher: IEEE.'},{id:"B21",body:'Wu H, Lin Q, You L. An investigation of the synchronous motor. In: Proceedings of the Fifth International Conference on Electrical Machines and Systems (ICEMs’ 01); 18-20 August 2001; Shenyang, China. pp. 148-151, Publisher: IEEE.'},{id:"B22",body:'Wang K, Zhu ZQ, Ombach G, Koch M, Zhang S, Xu J, Optimal slot/pole and flux-barrier layer number combinations for synchronous reluctance machines. In: Proceedings of the Eight International Conference and Exhibition on Ecological for Synchronous Reluctance Machines (EVER’ 13); 27-30 March 2013; Monte Carlo. pp. 1-8, Publisher: IEEE.'},{id:"B23",body:'Fukami T, Momiyama M, Shima K, Hanaoka R, Takata S. Steady-state analysis of a dual-winding reluctance generator with a multiple-barrier rotor. IEEE Transactions on Energy Conversion. 2008;23:492-498. DOI: 0.1109/TEC.2008.918656'},{id:"B24",body:'Bianchi N, Blognani S, Carraro E, Castiello M, Fornasiero E, Electric vehicle traction based on synchronous reluctance motors. IEEE Transaction on Industry Applications. 2016;52:4762-4769. DOI: 10.1109/TIA.2016.2599850'},{id:"B25",body:'Ehsani M, Gao Y, Gay S. Characterization of electric motor drive for traction applications. In: Proceedings of the IEEE 29th Annual Conference of the Industrial Electronics Society (IECON’03); Roanoke, USA. pp. 891-896'},{id:"B26",body:'Hangiu R.P, Martis C. A Review of Automotive Integrated Starter Alternators, The Scientific Bulletin of Electrical Engineering Faculty, 2012, p.1-6'},{id:"B27",body:'Yamanaka M, Koizumi H. A bi-directional Z-source inverter for electric vehicles. In: Proceedings of the International Conference on Power Electronics and Drive Systems (PEDS’09); 2-5 November 2009; Taipei, Taiwan. pp. 574-578, Publisher: IEEE.'},{id:"B28",body:'Cai W. Comparison and review of electric machines for integrated starter alternator applications. In: Proceedings of the 39th IAS Annual Meeting; 3-7 October 2004; Seattle, USA. pp. 386-393, Publisher: IEEE.'},{id:"B29",body:'Novotny DW, Lipo TA. Vector Control and Dynamics of AC Drives. Oxford: Clarendon Press; 1999. p. 464'},{id:"B30",body:'Ruba M, Jurca FN, Martis C. Analysis of Synchronous Reluctance Machine for Light Electric Vehicle Applications, In: Proceedings of the 2016 International Symposium on Power Electronics, Electrical Drives, Automation and Motion (SPEDAM ’16), 22-24 June 2016, Anacapri, Italy, pp. 1138-1143'},{id:"B31",body:'AMESim® User’s Guides [internet].https://www.plm.automation.siemens.com/en/products/lms/imagine-lab/amesim. Accessed: 2017-02-27.'},{id:"B32",body:'Electrical Specifications & Selection Guide Starter and Alternators-Delco Remy. 2008 [internet]. http://www.dieselusa.com/productinfo/Delco%20Electrical%20Specs%20and%20Seletion%20Guide.pdf. Accessed: 2016-08-12.'},{id:"B33",body:'Zhang X, Chris M. Vehicle Power Management. Berlin/Heidelberg: Springer-Verlag; 2011. p. 346'},{id:"B34",body:'Code of Federal Regulations, Title 40, Protection of Environment, Parts 425 to 699. US: Office of the Federal Register; 2010'},{id:"B35",body:'Jurca FN, Martis C, Hangiu RP. Design and performance analysis of an integrated starter-alternator for hybrid electric vehicles. In: Proceedings of the Interdisciplinary research in engineering: Steps towards breakthrough innovation for sustainable development. Advanced Engineering Forum. 2013;8-9:453-460'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Florin-Nicolae Jurca",address:"florin.jurca@emd.utcluj.ro",affiliation:'
Department of Electrical Machines and Drives, Technical University of Cluj-Napoca, Cluj-Napoca, Romania
Department of Electrical Machines and Drives, Technical University of Cluj-Napoca, Cluj-Napoca, Romania
'}],corrections:null},book:{id:"5910",title:"Hybrid Electric Vehicles",subtitle:null,fullTitle:"Hybrid Electric Vehicles",slug:"hybrid-electric-vehicles",publishedDate:"June 21st 2017",bookSignature:"Teresa Donateo",coverURL:"https://cdn.intechopen.com/books/images_new/5910.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"139190",title:"Prof.",name:"Teresa",middleName:null,surname:"Donateo",slug:"teresa-donateo",fullName:"Teresa Donateo"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"54808",title:"Trends and Hybridization Factor for Heavy-Duty Working Vehicles",slug:"trends-and-hybridization-factor-for-heavy-duty-working-vehicles",totalDownloads:2269,totalCrossrefCites:5,signatures:"Aurelio Somà",authors:[{id:"200187",title:"Prof.",name:"Aurelio",middleName:null,surname:"Soma'",fullName:"Aurelio Soma'",slug:"aurelio-soma'"}]},{id:"54787",title:"Development of Bus Drive Technology towards Zero Emissions: A Review",slug:"development-of-bus-drive-technology-towards-zero-emissions-a-review",totalDownloads:1587,totalCrossrefCites:1,signatures:"Julius Partridge, Wei Wu and Richard Bucknall",authors:[{id:"199365",title:"Ph.D. Student",name:"Wei",middleName:null,surname:"Wu",fullName:"Wei Wu",slug:"wei-wu"},{id:"205711",title:"Dr.",name:"Julius",middleName:null,surname:"Partridge",fullName:"Julius Partridge",slug:"julius-partridge"},{id:"205712",title:"Dr.",name:"Richard",middleName:null,surname:"Bucknall",fullName:"Richard Bucknall",slug:"richard-bucknall"}]},{id:"55824",title:"Advanced Charging System for Plug-in Hybrid Electric Vehicles and Battery Electric Vehicles",slug:"advanced-charging-system-for-plug-in-hybrid-electric-vehicles-and-battery-electric-vehicles",totalDownloads:2006,totalCrossrefCites:6,signatures:"Muhammad Aziz",authors:[{id:"98160",title:"Associate Prof.",name:"Muhammad",middleName:null,surname:"Aziz",fullName:"Muhammad Aziz",slug:"muhammad-aziz"}]},{id:"54471",title:"A Hybrid Energy Storage System for a Coaxial Power-Split Hybrid Powertrain",slug:"a-hybrid-energy-storage-system-for-a-coaxial-power-split-hybrid-powertrain",totalDownloads:1668,totalCrossrefCites:1,signatures:"Enhua Wang, Fuyuan Yang and Minggao Ouyang",authors:[{id:"199752",title:"Dr.",name:"Enhua",middleName:null,surname:"Wang",fullName:"Enhua Wang",slug:"enhua-wang"},{id:"200815",title:"Prof.",name:"Fuyuan",middleName:null,surname:"Yang",fullName:"Fuyuan Yang",slug:"fuyuan-yang"},{id:"200816",title:"Prof.",name:"Minggao",middleName:null,surname:"Ouyang",fullName:"Minggao Ouyang",slug:"minggao-ouyang"}]},{id:"55341",title:"Performance Analysis of an Integrated Starter-Alternator- Booster for Hybrid Electric Vehicles",slug:"performance-analysis-of-an-integrated-starter-alternator-booster-for-hybrid-electric-vehicles",totalDownloads:1505,totalCrossrefCites:0,signatures:"Florin-Nicolae Jurca and Mircea Ruba",authors:[{id:"180939",title:"Dr.",name:"Nicolae Florin",middleName:null,surname:"Jurca",fullName:"Nicolae Florin Jurca",slug:"nicolae-florin-jurca"},{id:"190371",title:"Dr.",name:"Mircea",middleName:null,surname:"Ruba",fullName:"Mircea Ruba",slug:"mircea-ruba"}]},{id:"54916",title:"Design, Optimization and Modelling of High Power Density Direct-Drive Wheel Motor for Light Hybrid Electric Vehicles",slug:"design-optimization-and-modelling-of-high-power-density-direct-drive-wheel-motor-for-light-hybrid-el",totalDownloads:2194,totalCrossrefCites:3,signatures:"Ioannis D. Chasiotis and Yannis L. Karnavas",authors:[{id:"201051",title:"Prof.",name:"Yannis",middleName:"L",surname:"Karnavas",fullName:"Yannis Karnavas",slug:"yannis-karnavas"},{id:"201532",title:"MSc.",name:"Ioannis",middleName:null,surname:"Chasiotis",fullName:"Ioannis Chasiotis",slug:"ioannis-chasiotis"}]}]},relatedBooks:[{type:"book",id:"19",title:"New Trends and Developments in Automotive System Engineering",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"new-trends-and-developments-in-automotive-system-engineering",bookSignature:"Marcello Chiaberge",coverURL:"https://cdn.intechopen.com/books/images_new/19.jpg",editedByType:"Edited by",editors:[{id:"13723",title:"Prof.",name:"Marcello",surname:"Chiaberge",slug:"marcello-chiaberge",fullName:"Marcello Chiaberge"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"13344",title:"Experimental Test of a Diesel Engine Using Envo-Diesel as an Alternative Fuel",slug:"experimental-test-of-a-diesel-engine-using-envo-diesel-as-an-alternative-fuel",signatures:"M.A.Kalam and H.H. Masjuki",authors:[{id:"13349",title:"Dr.",name:"Md Abul",middleName:null,surname:"Kalam",fullName:"Md Abul Kalam",slug:"md-abul-kalam"}]},{id:"13345",title:"Analytical Methods for Determining Automotive Fuel Composition",slug:"analytical-methods-for-determining-automotive-fuel-composition",signatures:"Jonas Gruber, Renata Lippi, Rosamaria W. C. Li and Adriano R. V. Benvenho",authors:[{id:"13765",title:"Dr.",name:"Jonas",middleName:null,surname:"Gruber",fullName:"Jonas Gruber",slug:"jonas-gruber"},{id:"14795",title:"Dr.",name:"Adriano R. V.",middleName:null,surname:"Benvenho",fullName:"Adriano R. V. Benvenho",slug:"adriano-r.-v.-benvenho"},{id:"14796",title:"Dr.",name:"Rosamaria W. C.",middleName:null,surname:"Li",fullName:"Rosamaria W. C. Li",slug:"rosamaria-w.-c.-li"},{id:"14797",title:"Prof.",name:"Renata",middleName:null,surname:"Lippi",fullName:"Renata Lippi",slug:"renata-lippi"}]},{id:"13346",title:"Automotive Fuel Consumption in Brazil: Applying Static and Dynamic Systems of Demand Equations",slug:"automotive-fuel-consumption-in-brazil-applying-static-and-dynamic-systems-of-demand-equations",signatures:"Mariana Iootty, Helder Pinto Jr. and Francisco Ebeling",authors:[{id:"13948",title:"Dr.",name:"Francisco",middleName:null,surname:"Ebeling",fullName:"Francisco Ebeling",slug:"francisco-ebeling"},{id:"13951",title:"Prof.",name:"Mariana",middleName:null,surname:"Iootty",fullName:"Mariana Iootty",slug:"mariana-iootty"},{id:"13952",title:"Prof.",name:"Helder",middleName:"Queiroz",surname:"Pinto, Jr.",fullName:"Helder Pinto, Jr.",slug:"helder-pinto-jr."}]},{id:"13347",title:"Fatigue and Fracture Behavior of Forging Die Steels",slug:"fatigue-and-fracture-behavior-of-forging-die-steels",signatures:"Ryuichiro Ebara",authors:[{id:"13816",title:"Prof.",name:"Ryuichiro",middleName:null,surname:"Ebara",fullName:"Ryuichiro Ebara",slug:"ryuichiro-ebara"}]},{id:"13348",title:"Optimization of Injection Moulded Polymer Automotive Components",slug:"optimization-of-injection-moulded-polymer-automotive-components",signatures:"Ribeiro, C.J. and Viana, J.C.",authors:[{id:"15565",title:"Prof.",name:"Julio",middleName:null,surname:"Viana",fullName:"Julio Viana",slug:"julio-viana"},{id:"17010",title:"Prof.",name:"Carlos",middleName:null,surname:"Ribeiro",fullName:"Carlos Ribeiro",slug:"carlos-ribeiro"}]},{id:"13349",title:"High Mn TWIP Steels for Automotive Applications",slug:"high-mn-twip-steels-for-automotive-applications",signatures:"B. C. De Cooman, Kwang-geun Chin and Jinkyung Kim",authors:[{id:"16743",title:"Prof.",name:"Bruno Charles",middleName:null,surname:"De Cooman",fullName:"Bruno Charles De Cooman",slug:"bruno-charles-de-cooman"}]},{id:"13350",title:"Powder Injection Moulding - An Alternative Processing Method for Automotive Items",slug:"powder-injection-moulding-an-alternative-processing-method-for-automotive-items",signatures:"Berenika Hausnerova",authors:[{id:"13927",title:"Dr.",name:"Berenika",middleName:null,surname:"Hausnerova",fullName:"Berenika Hausnerova",slug:"berenika-hausnerova"}]},{id:"13351",title:"Thermomechanical and Isothermal Fatigue Behavior of Gray Cast Iron for Automotive Brake Discs",slug:"thermomechanical-and-isothermal-fatigue-behavior-of-gray-cast-iron-for-automotive-brake-discs",signatures:"Omar Maluf, Jéferson Aparecido Moreto, Maurício Angeloni, Marco Antônio Colósio, José Carlos Santos, Waldek Wladimir Bose Filho and Dirceu Spinelli",authors:[{id:"16423",title:"Dr.",name:"Omar",middleName:null,surname:"Maluf",fullName:"Omar Maluf",slug:"omar-maluf"},{id:"16672",title:"Dr.",name:"Jéferson Aparecido",middleName:null,surname:"Moreto",fullName:"Jéferson Aparecido Moreto",slug:"jeferson-aparecido-moreto"},{id:"16673",title:"Dr.",name:"Marco Antônio",middleName:null,surname:"Colósio",fullName:"Marco Antônio Colósio",slug:"marco-antonio-colosio"},{id:"16674",title:"MSc",name:"José Carlos",middleName:null,surname:"Santos",fullName:"José Carlos Santos",slug:"jose-carlos-santos"},{id:"16675",title:"Dr.",name:"Waldek Wladimir",middleName:null,surname:"Bose Filho",fullName:"Waldek Wladimir Bose Filho",slug:"waldek-wladimir-bose-filho"},{id:"16676",title:"Dr.",name:"Dirceu",middleName:null,surname:"Spinelli",fullName:"Dirceu Spinelli",slug:"dirceu-spinelli"},{id:"23757",title:"Dr.",name:"Mauricio",middleName:null,surname:"Angeloni",fullName:"Mauricio Angeloni",slug:"mauricio-angeloni"}]},{id:"13352",title:"Advanced Robotic Radiative Process Control for Automotive Coatings",slug:"advanced-robotic-radiative-process-control-for-automotive-coatings",signatures:"Fan Zeng and Beshah Ayalew",authors:[{id:"14308",title:"Dr.",name:"Fan",middleName:null,surname:"Zeng",fullName:"Fan Zeng",slug:"fan-zeng"},{id:"15317",title:"Dr.",name:"Beshah",middleName:null,surname:"Ayalew",fullName:"Beshah Ayalew",slug:"beshah-ayalew"}]},{id:"13353",title:"DC/DC Step-Up Converters for Automotive Applications: a FPGA Based Approach",slug:"dc-dc-step-up-converters-for-automotive-applications-a-fpga-based-approach",signatures:"M. Chiaberge, G. Botto and M. De Giuseppe",authors:[{id:"13723",title:"Prof.",name:"Marcello",middleName:null,surname:"Chiaberge",fullName:"Marcello Chiaberge",slug:"marcello-chiaberge"},{id:"14730",title:"Prof.",name:"Gianluca",middleName:null,surname:"Botto",fullName:"Gianluca Botto",slug:"gianluca-botto"},{id:"14731",title:"Prof.",name:"Mirko",middleName:null,surname:"De Giuseppe",fullName:"Mirko De Giuseppe",slug:"mirko-de-giuseppe"}]},{id:"13354",title:"The Thermo-Mechanical Behavior in Automotive Brake and Clutch Systems",slug:"the-thermo-mechanical-behavior-in-automotive-brake-and-clutch-systems",signatures:"Abdullah M. Al-Shabibi",authors:[{id:"13352",title:"Dr.",name:"Abdullah",middleName:null,surname:"Al-Shabibi",fullName:"Abdullah Al-Shabibi",slug:"abdullah-al-shabibi"}]},{id:"13355",title:"Dynamic Analysis of an Automobile Lower Suspension Arm Using Experiment and Numerical Technique",slug:"dynamic-analysis-of-an-automobile-lower-suspension-arm-using-experiment-and-numerical-technique",signatures:"S. Abdullah, N.A. Kadhim, A.K. Ariffin and M. Hosseini",authors:[{id:"14658",title:"Dr.",name:"N.",middleName:"A.",surname:"Kadhim",fullName:"N. Kadhim",slug:"n.-kadhim"},{id:"15142",title:"Dr.",name:"Shahrum",middleName:null,surname:"Abdullah",fullName:"Shahrum Abdullah",slug:"shahrum-abdullah"},{id:"15143",title:"Prof.",name:"A.K.",middleName:null,surname:"Ariffin",fullName:"A.K. Ariffin",slug:"a.k.-ariffin"}]},{id:"13356",title:"Increased Cooling Power with Nucleate Boiling Flow in Automotive Engine Applications",slug:"increased-cooling-power-with-nucleate-boiling-flow-in-automotive-engine-applications",signatures:"Helfried Steiner, Günter Brenn, Franz Ramstorfer and Bernd Breitschädel",authors:[{id:"14874",title:"Dr.",name:"Helfried",middleName:null,surname:"Steiner",fullName:"Helfried Steiner",slug:"helfried-steiner"},{id:"14883",title:"Prof.",name:"Günter",middleName:null,surname:"Brenn",fullName:"Günter Brenn",slug:"gunter-brenn"},{id:"14884",title:"Dr.",name:"Franz",middleName:null,surname:"Ramstorfer",fullName:"Franz Ramstorfer",slug:"franz-ramstorfer"},{id:"14885",title:"Dr.",name:"Bernd",middleName:null,surname:"Breitschädel",fullName:"Bernd Breitschädel",slug:"bernd-breitschadel"}]},{id:"13357",title:"The 'Equivalent Cable Bundle Method': an Efficient Multiconductor Reduction Technique to Model Industrial Cable Networks",slug:"the-equivalent-cable-bundle-method-an-efficient-multiconductor-reduction-technique-to-model-industri",signatures:"Guillaume Andrieu, Xavier Bunlon, Lamine Koné, Jean-Philippe Parmantier, Bernard Démoulin and Alain Reineixl",authors:[{id:"13883",title:"Dr.",name:"Guillaume",middleName:null,surname:"Andrieu",fullName:"Guillaume Andrieu",slug:"guillaume-andrieu"}]},{id:"13358",title:"Fatigue Characteristics of Automotive Jounce Bumper",slug:"fatigue-characteristics-of-automotive-jounce-bumper",signatures:"Aidy Ali, R.S. Sidhu and M.S.A. Samad",authors:[{id:"13626",title:"Prof.",name:"Aidy",middleName:null,surname:"Ali",fullName:"Aidy Ali",slug:"aidy-ali"}]},{id:"13359",title:"On the Control of Automotive Traction PEM Fuel Cell Systems",slug:"on-the-control-of-automotive-traction-pem-fuel-cell-systems",signatures:"Ahmed Al-Durra, Stephen Yurkovich and Yann Guezennec",authors:[{id:"13634",title:"Dr.",name:"Ahmed",middleName:null,surname:"Al-Durra",fullName:"Ahmed Al-Durra",slug:"ahmed-al-durra"},{id:"14586",title:"Prof.",name:"Stephen",middleName:null,surname:"Yurkovich",fullName:"Stephen Yurkovich",slug:"stephen-yurkovich"},{id:"14587",title:"Prof.",name:"Yann",middleName:null,surname:"Guezennec",fullName:"Yann Guezennec",slug:"yann-guezennec"}]},{id:"13360",title:"An Adaptive Two-Stage Observer in the Control of a New Electromagnetic Valve Actuator for Camless Internal Combustion Engines",slug:"an-adaptive-two-stage-observer-in-the-control-of-a-new-electromagnetic-valve-actuator-for-camless-in",signatures:"Paolo Mercorelli",authors:[{id:"13488",title:"Prof.",name:"Paolo",middleName:null,surname:"Mercorelli",fullName:"Paolo Mercorelli",slug:"paolo-mercorelli"}]},{id:"13361",title:"Integrated Controller Design for Automotive Semi-Active Suspension Considering Vehicle Behavior with Steering Input",slug:"integrated-controller-design-for-automotive-semi-active-suspension-considering-vehicle-behavior-with",signatures:"Masaki Takahashi, Takashi Kumamaru and Kazuo Yoshida",authors:[{id:"6184",title:"Prof.",name:"Masaki",middleName:null,surname:"Takahashi",fullName:"Masaki Takahashi",slug:"masaki-takahashi"},{id:"17387",title:"Prof.",name:"Takashi",middleName:null,surname:"Kumamaru",fullName:"Takashi Kumamaru",slug:"takashi-kumamaru"},{id:"17388",title:"Prof.",name:"Kazuo",middleName:null,surname:"Yoshida",fullName:"Kazuo Yoshida",slug:"kazuo-yoshida"}]},{id:"13362",title:"Design of an Embedded Controller for Some Applications of an Automotives",slug:"design-of-an-embedded-controller-for-some-applications-of-an-automotives",signatures:"Preeti Bajaj and Dinesh Padole",authors:[{id:"23615",title:"Dr.",name:"Preeti",middleName:null,surname:"Bajaj",fullName:"Preeti Bajaj",slug:"preeti-bajaj"},{id:"23618",title:"Prof.",name:"Dinesh",middleName:null,surname:"Padole",fullName:"Dinesh Padole",slug:"dinesh-padole"}]},{id:"13363",title:"Arbitration Schemes for Multiprocessor Shared Bus",slug:"arbitration-schemes-for-multiprocessor-shared-bus",signatures:"Preeti Bajaj and Dinesh Padole",authors:[{id:"23615",title:"Dr.",name:"Preeti",middleName:null,surname:"Bajaj",fullName:"Preeti Bajaj",slug:"preeti-bajaj"},{id:"23618",title:"Prof.",name:"Dinesh",middleName:null,surname:"Padole",fullName:"Dinesh Padole",slug:"dinesh-padole"}]},{id:"13364",title:"Towards Automotive Embedded Systems with Self-X Properties",slug:"towards-automotive-embedded-systems-with-self-x-properties",signatures:"Gereon Weiss, Marc Zeller and Dirk Eilers",authors:[{id:"15139",title:"M.Sc.",name:"Gereon",middleName:null,surname:"Weiss",fullName:"Gereon Weiss",slug:"gereon-weiss"},{id:"15151",title:"MSc.",name:"Marc",middleName:null,surname:"Zeller",fullName:"Marc Zeller",slug:"marc-zeller"},{id:"15152",title:"Dr.",name:"Dirk",middleName:null,surname:"Eilers",fullName:"Dirk Eilers",slug:"dirk-eilers"}]},{id:"13365",title:"4D Ground Plane Estimation Algorithm for Advanced Driver Assistance Systems",slug:"4d-ground-plane-estimation-algorithm-for-advanced-driver-assistance-systems",signatures:"Faisal Mufti, Robert Mahony and Jochen Heinzmann",authors:[{id:"14155",title:"Dr.",name:"Faisal",middleName:null,surname:"Mufti",fullName:"Faisal Mufti",slug:"faisal-mufti"},{id:"15158",title:"Dr.",name:"Robert",middleName:null,surname:"Mahony",fullName:"Robert Mahony",slug:"robert-mahony"},{id:"15159",title:"Dr.",name:"Jochen",middleName:null,surname:"Heinzmann",fullName:"Jochen Heinzmann",slug:"jochen-heinzmann"}]},{id:"13366",title:"The Car Entertainment System",slug:"the-car-entertainment-system",signatures:"Niels Koch",authors:[{id:"13732",title:"Dr.",name:"Niels",middleName:null,surname:"Koch",fullName:"Niels Koch",slug:"niels-koch"}]},{id:"13367",title:"Information and Communication Support for Automotive Testing and Validation",slug:"information-and-communication-support-for-automotive-testing-and-validation",signatures:"Mathias Johanson",authors:[{id:"13572",title:"Dr.",name:"Mathias",middleName:null,surname:"Johanson",fullName:"Mathias Johanson",slug:"mathias-johanson"}]},{id:"13368",title:"Trends Towards Automotive Electronic Vision Systems for Mitigation of Accidents in Safety Critical Situations",slug:"trends-towards-automotive-electronic-vision-systems-for-mitigation-of-accidents-in-safety-critical-s",signatures:"Ciarán Hughes, Ronan O’Malley, Diarmaid O’Cualain, Martin Glavin and Edward Jones",authors:[{id:"13452",title:"Dr.",name:"Ciaran",middleName:null,surname:"Hughes",fullName:"Ciaran Hughes",slug:"ciaran-hughes"},{id:"14934",title:"Prof.",name:"Ronan",middleName:null,surname:"O’Malley",fullName:"Ronan O’Malley",slug:"ronan-o'malley"},{id:"14935",title:"Mr",name:"Diarmaid",middleName:null,surname:"O'Cualain",fullName:"Diarmaid O'Cualain",slug:"diarmaid-o'cualain"},{id:"14936",title:"Dr.",name:"Martin",middleName:null,surname:"Glavin",fullName:"Martin Glavin",slug:"martin-glavin"},{id:"14937",title:"Dr.",name:"Edward",middleName:null,surname:"Jones",fullName:"Edward Jones",slug:"edward-jones"}]},{id:"13369",title:"Advancements in Automotive Antennas",slug:"advancements-in-automotive-antennas",signatures:"Brendan D. Pell, Edin Sulic, Wayne S. T. Rowe, Kamran Ghorbani and Sabu John",authors:[{id:"14535",title:"Prof.",name:"Brendan",middleName:"David",surname:"Pell",fullName:"Brendan Pell",slug:"brendan-pell"},{id:"24315",title:"Dr.",name:"Wayne",middleName:null,surname:"Rowe",fullName:"Wayne Rowe",slug:"wayne-rowe"},{id:"24316",title:"Mr.",name:"Edin",middleName:null,surname:"sulic",fullName:"Edin sulic",slug:"edin-sulic"},{id:"24317",title:"Dr.",name:"Kamran",middleName:null,surname:"Ghorbani",fullName:"Kamran Ghorbani",slug:"kamran-ghorbani"},{id:"24318",title:"Prof.",name:"Sabu",middleName:null,surname:"John",fullName:"Sabu John",slug:"sabu-john"}]},{id:"13370",title:"Automotive VHDL-AMS Electro-Mechanics Simulations",slug:"automotive-vhdl-ams-electro-mechanics-simulations",signatures:"Mariagrazia Graziano and Massimo Ruo Roch",authors:[{id:"13960",title:"Dr.",name:"Mariagrazia",middleName:null,surname:"Graziano",fullName:"Mariagrazia Graziano",slug:"mariagrazia-graziano"},{id:"13961",title:"Dr.",name:"Massimo",middleName:null,surname:"Ruo Roch",fullName:"Massimo Ruo Roch",slug:"massimo-ruo-roch"}]},{id:"13371",title:"Potential and Drawbacks of Raman (Micro)spectrometry for the Understanding of Iron and Steel Corrosion",slug:"potential-and-drawbacks-of-raman-micro-spectrometry-for-the-understanding-of-iron-and-steel-corrosio",signatures:"Philippe Colomban",authors:[{id:"14026",title:"Dr.",name:"Philippe",middleName:null,surname:"Colomban",fullName:"Philippe Colomban",slug:"philippe-colomban"}]},{id:"13372",title:"Computational Techniques for Automotive Antenna Simulations",slug:"computational-techniques-for-automotive-antenna-simulations",signatures:"Faik Bogdanov, Roman Jobava, David Karkashadze, Paata Tsereteli, Anna Gheonjian, Ekaterina Yavolovskaya, Detlef Schleicher, Christoph Ullrich and Hicham Tazi",authors:[{id:"13734",title:"Dr.",name:"Faik",middleName:null,surname:"Bogdanov",fullName:"Faik Bogdanov",slug:"faik-bogdanov"},{id:"14889",title:"Prof.",name:"Roman",middleName:null,surname:"Jobava",fullName:"Roman Jobava",slug:"roman-jobava"},{id:"17047",title:"Dr.",name:"David",middleName:null,surname:"Karkashadze",fullName:"David Karkashadze",slug:"david-karkashadze"},{id:"17050",title:"Dr.",name:"Paata",middleName:null,surname:"Tsereteli",fullName:"Paata Tsereteli",slug:"paata-tsereteli"},{id:"17052",title:"Ms.",name:"Anna",middleName:null,surname:"Gheonjian",fullName:"Anna Gheonjian",slug:"anna-gheonjian"},{id:"17053",title:"Ms.",name:"Ekaterina",middleName:null,surname:"Yavolovskaya",fullName:"Ekaterina Yavolovskaya",slug:"ekaterina-yavolovskaya"},{id:"17055",title:"Dr.",name:"Christoph",middleName:null,surname:"Ullrich",fullName:"Christoph Ullrich",slug:"christoph-ullrich"},{id:"17056",title:"Ms.",name:"Hicham",middleName:null,surname:"Tazi",fullName:"Hicham Tazi",slug:"hicham-tazi"},{id:"17063",title:"Dr.",name:"Detlef",middleName:null,surname:"Schleicher",fullName:"Detlef Schleicher",slug:"detlef-schleicher"}]},{id:"13373",title:"Voltage Stability Analysis of Automotive Power Nets based on Modeling and Experimental Results",slug:"voltage-stability-analysis-of-automotive-power-nets-based-on-modeling-and-experimental-results",signatures:"Tom P. Kohler, Rainer Gehring, Joachim Froeschl, Dominik Buecherl and Hans-Georg Herzog",authors:[{id:"13880",title:"Prof.",name:"Tom P.",middleName:null,surname:"Kohler",fullName:"Tom P. Kohler",slug:"tom-p.-kohler"},{id:"15218",title:"Mr.",name:"Rainer",middleName:null,surname:"Gehring",fullName:"Rainer Gehring",slug:"rainer-gehring"},{id:"15219",title:"Mr.",name:"Joachim",middleName:null,surname:"Froeschl",fullName:"Joachim Froeschl",slug:"joachim-froeschl"},{id:"15220",title:"Prof.",name:"Dominik",middleName:null,surname:"Buecherl",fullName:"Dominik Buecherl",slug:"dominik-buecherl"},{id:"15221",title:"Prof.",name:"Hans-Georg",middleName:null,surname:"Herzog",fullName:"Hans-Georg Herzog",slug:"hans-georg-herzog"}]},{id:"13374",title:"Urban and Extra Urban Vehicles: Re-Thinking the Vehicle Design",slug:"urban-and-extra-urban-vehicles-re-thinking-the-vehicle-design",signatures:"Andrea Festini, Andrea Tonoli and Enrico Zenerino",authors:[{id:"13723",title:"Prof.",name:"Marcello",middleName:null,surname:"Chiaberge",fullName:"Marcello Chiaberge",slug:"marcello-chiaberge"},{id:"14732",title:"Prof.",name:"Andrea",middleName:null,surname:"Festini",fullName:"Andrea Festini",slug:"andrea-festini"},{id:"14733",title:"Dr.Ing.",name:"Enrico",middleName:null,surname:"Zenerino",fullName:"Enrico Zenerino",slug:"enrico-zenerino"},{id:"14734",title:"Prof.",name:"Andrea",middleName:null,surname:"Tonoli",fullName:"Andrea Tonoli",slug:"andrea-tonoli"}]},{id:"13375",title:"Analysis Approach of How University Automotive Competitions Help Students to Accelerate their Automotive Engineer Profile",slug:"analysis-approach-of-how-university-automotive-competitions-help-students-to-accelerate-their-automo",signatures:"Francisco J. Sánchez-Alejo, Miguel A. Álvarez, Francisco Aparicio and José M. López",authors:[{id:"10792",title:"Dr.",name:"José Mª",middleName:null,surname:"Lopez",fullName:"José Mª Lopez",slug:"jose-ma-lopez"},{id:"13917",title:"Dr.",name:"Francisco J.",middleName:null,surname:"Sánchez-Alejo",fullName:"Francisco J. Sánchez-Alejo",slug:"francisco-j.-sanchez-alejo"},{id:"15271",title:"Ing.",name:"Miguel A.",middleName:null,surname:"Alvarez",fullName:"Miguel A. Alvarez",slug:"miguel-a.-alvarez"},{id:"15272",title:"Dr.",name:"Francisco",middleName:null,surname:"Aparicio",fullName:"Francisco Aparicio",slug:"francisco-aparicio"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"66194",title:"Targeting Peptides Derived from Phage Display for Clinical Imaging",doi:"10.5772/intechopen.84281",slug:"targeting-peptides-derived-from-phage-display-for-clinical-imaging",body:'\n
\n
1. Introduction
\n
One of the most important practices in modern era clinical imaging is imaging at the molecular level which can help characterize and measure in vivo biological processes at the cellular level [1]. Thus, the technique provides unambiguous and high-resolution real-time information for disease diagnoses and therapies. In addition, molecular imaging is usually noninvasive as a biologically active, receptor-specific, targeting vector conjugated to a radioligand, nanoparticle, and/or fluorescent/magnetic resonance imaging (MRI) probe is administered first, and then the probe signals can be quantified by positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), fluorescence imaging, or ultrasound. The specificity of probes may be contributed from targeting peptides, small proteins, and antibodies linked to the probes [2].
\n
One of the most important aspects in successful molecular imaging is the development of imaging probes. Initial efforts focused on probes that are radiolabeled small molecules or macromolecules, e.g., monoclonal antibodies and their fragments [3]. Most such probes are unsuccessful because small molecules provide low specificity, whereas the antibodies have low target permeability. Taken into account altogether, these probes have low contrast between target tissues and background, leading to poor imaging qualities. Compared to small molecules and antibodies, peptide imaging probes are more promising. The peptide length varies from several to approximately 50 amino acids [4]; thus they are usually more specific than small molecules and also more permeable than antibodies. The peptides have high capillary permeability, which allows efficient penetration into tissues. In addition, they also have high uptake rates in the target and rapid clearance from blood [1]. These distinctive advantages facilitate peptides as popular imaging probes. Such a probe is usually composed of a targeting peptide, a linker, and an imaging moiety. The linkers commonly are organic spacers, macrocyclic or branched chelators, and polymers, which link peptides with appropriate moieties. Different moieties render the probes observable by various devices, e.g., near-infrared (NIR) fluorescent dyes or quantum dots for optical imaging, radionuclides for PET or SPECT, and paramagnetic agents for MRI.
\n
Phage display technology is a powerful approach to screen for peptides with high affinities and specificities to biomarkers. This technology was established by Smith et al. in 1985 to display polypeptides on the surface of filamentous M13-derived bacteriophage (phage) [5]. This technique modifies the phage genome to fuse the deoxyribonucleic acid (DNA) encoding a peptide to a gene encoding a protein comprising the phage coat; thus the peptide appears on the surface of the phage. In this way, each phage contains a single-peptide variant and its encoding DNA sequence, thus retaining a genotype-phenotype linkage. A library or pool of phages normally contains 109–1011 peptide variants for screening. The selection procedure consists of three main steps: (1) panning the pool of phages on the immobilized biomarker, (2) removing unbound phages by washing, and (3) elution of bound phages. After several rounds of such selections, the peptide sequences with high affinities to the biomarker are determined by sequencing the encoding DNAs in the phages. Specificity of the peptides can be also improved by adding extra negative selection steps [6].
\n
Since its inception nearly 45 years ago, phage display has been widely used in thousands of research papers to isolate peptides that bind various targets [7]. The phage peptides are labeled with imaging agents such as radioactives, fluorescences, and nanoparticles. These probes have been successfully used to image tumors and cancers [8, 9, 10]. Moreover, phage display also influenced many other scientific fields such as drug discovery, vaccine development, and targeted drug delivery and gene therapy. With advances in molecular biology, the number of disease-associated biomarkers at the molecular level is ever-increasing. These new discoveries are motivating the applications of phage display to diagnostic imaging and targeted drug delivery.
\n
\n
\n
2. Phage biology and phage selection screening methods
\n
\n
2.1 Phage biology
\n
Bacteriophages (or phages) are viruses that infect bacteria. Phage virions vary widely in size, shape, and complexity, and phage genomes range in size from 3.4 kb to almost 500 kb [11]. Most phage genomes (>95%) discovered to date are linear, double-stranded DNAs (dsDNAs), but there are also genomes that are single-stranded DNAs (ssDNA), circular DNAs, and RNAs [12]. The phage genome is packed into a protein capsid, which together form a phage particle. Some phages, such as pleomorphic phages, are further covered by bacterial lipoprotein membrane during budding [13]. As a parasite, the phage life cycle is intertwined with that of the host cell, i.e., bacteria. The phage particle first attaches itself to a host cell by specific recognition of a receptor or other surface moiety of the host; then the phage nucleic acids are inserted into the host cell. Inside the host cell, the phage genome shuts down defense mechanisms of the host and hijacks host cellular components to replicate phage genome and express capsid genes from the phage genome. Eventually, phage genomes and capsids are assembled into progeny phage particles. These phage particles emerge from the host cell, which usually results in cell lysis by phage proteins (Figure 1).
\n
Figure 1.
A scheme presents lytic and lysogenic stages of phage.
\n
Phages were discovered by Twort in 1915 and d’Hérelle in 1917 [12], respectively. Now, it is clear that phages are the most abundant organisms on the earth; they have been found in every environment with bacteria. An estimated 1031 phage particles exist on earth. Since the 1940s, phages have been model organisms and have contributed to molecular biology substantially. The most remarkable contributions include revealing the random nature of mutation, the discovery of DNA as the genetic material, and the understanding of gene expression control. With advances in biotechnology, phage display was established by Smith in 1985.
\n
In phage display, the most widely used phage is the M13 strain of filamentous bacteriophage. This type of phage infects F plasmid-containing gram-negative bacteria, such as Escherichia coli. Besides M13, other members of filamentous phages such as f1 and fd strains have also been used for phage display [14]. These phages have circular single-stranded DNA (ssDNA). The genome is composed of 11 genes [15], which are classified into three groups by functions. The first group comprises capsid proteins: protein III (pIII), pVI, pVII, pVIII, and pIX; the second group is for DNA replication, pII, pV, and pX; the last group consists of proteins for assembly, pI, pIV, and pXI. This genome is contained in a protein coat to form a phage particle of 6.5 nm in width and ~900 nm in length. Normally, filamentous phage is not lytic; thus phages are released from bacteria without bacterial lysis. Instead of phage M13, phage display can also use phagemid, which is simply a plasmid with a phage origin of replication so that the plasmid can be replicated and packaged into phage particles. The phagemid as a cloning vector needs helper phage to complete its infection process and virion packaging [16].
\n
\n
\n
2.2 Phage selection screening methods
\n
\n
2.2.1 Peptide library
\n
Peptide library construction is the first step in selecting peptides with high affinities to the target of interest. Each of the 20 amino acids is encoded by codons, and each codon consists of three consecutive nucleotides. There are four types of nucleotides, denoted as A (adenine), G (guanine), C (cytosine), and T (thymine). A random peptide is constructed by synthesizing an oligonucleotide containing (NNK)n, where N stands for any of the four nucleotides, K stands for either G or T, and n indicates the desired length of the peptide. Note that only G or T is introduced to the third position of a codon because this reduces the frequency of stop codons (NNN generates three stop codons: TAA, TGA and TAG, whereas NNK generates only one codon: TAG). To add a site with N, simply provide an equimolar mixture of A, T, G, and C, and randomly one of them is added at the end of the nucleotide chain. As for a site with K, just provide a mixture of G and T to the reaction [17]. In this way, numerous oligonucleotides are synthesized in parallel, and each oligonucleotide encodes a random peptide. Note that the NNK codon pattern is generated by controlling nucleotide types to be added in reactions. This simple rule can be modified to create particular codons, e.g., allowing no stop codon or creating codons of charged residues.
\n
Peptide libraries often have short peptide lengths, approximately less than 50 residues. The optimum length required for the randomized displayed peptide is often unknown before selection and varies with many factors including the folding properties of the displayed peptide and the target of interest. For a library of random peptides with seven residues, the maximum number of different peptides is 207. However, this number is usually unapproachable due to codon degeneracy and early stop codon. In other words, a library usually contains redundant peptides and peptides shorter than desired. On the other hand, the capacity of selection is limited by transfection, i.e., only 108–1010 phages, each encloses one peptide, can be transformed into E. coli by electroporation or other techniques. Taken together, the diversity of a library is important for the success of selection and screening for high affinity peptides. A typical commercially available library archives peptide diversity at the level of 109 [4].
\n
In M13 phage, the oligonucleotides encoding random peptides are mostly fused to the N-terminus of pIII, with a spacer as a linker to generate a phage library. Another widely used gene for peptide display is the one encoding pVIII. Both pIII and pVIII are the major and minor capsid proteins, accessible from the outer surface of the phage. pIII has 406 residues, and for each phage, there are in total 3–5 pIII proteins which form a knob-like structure at one end of the phage. This structure is responsible for infection of bacteria via the F-pilus, virion stability, and assembly termination. The peptides linked to pIII for display almost have no restriction on length, facilitating pIII as the mostly targeted for peptide display applications. As for pVIII, it is a short helical protein (50 residues) [18], and about 2700 pVIII molecules are present on the capsid. However, only the three residues at the N-terminus are accessible from the outer surface of the phage. Unlike pIII, pVIII can tolerate only short peptides with less than ten residues to be linked and successfully displayed, which is likely due to interrupted assembly by long peptides. However, this problem can be alleviated by reducing the density of pVIII mutants [19]. Interestingly, some other capsid proteins such as pV1, pVII, and pIX have poorer accessibilities on the phage surface but nevertheless successfully display peptides for screening [19].
\n
\n
\n
2.2.2 In vitro screening
\n
In a phage library, each of the trillion phages displays a single variant of random peptides on its surface. Many methods have been developed to identify the peptides that have high affinities to the target of interest, e.g., a biomarker protein. To this end, biopanning is the most commonly used method, and it has many variations to improve the performance of selection and screening or to accommodate for special targets [20].
\n
Biopanning consists of four basic steps: (i) target immobilization, (ii) phage binding, (iii) washing, and (iv) phage elution. In the first step, the target of interest is purified and immobilized on plates. Some targets are not able to maintain structural integrity after being separated from cells, e.g., some transmembrane proteins. Therefore, whole cells or engineered cells may instead be immobilized on plates or suspended in solutions in this step [21]. In phage binding, the phages in a library are incubated with the plate, and appropriate buffers are also added to facilitate the binding reactions between the displayed peptides on phages and the targets on plates. After that, the plates are washed to remove unbound phages. Phage elution is to acquire the bound phages by disrupting the interaction between the peptides and the targets. This disruption is conducted by changing pH or adding competing ligands, denaturant, or protease. The eluted phages are amplified by infecting E. coli. The phages may go through another round of biopanning or are subject to DNA sequencing to determine the peptide sequences (Figure 2). These peptides are considered to possess high affinities to the target.
\n
Figure 2.
General scheme of affinity selection of target-specific peptides.
\n
Following several rounds of biopanning, the selected peptides have high affinities to the target but may not have high specificities, i.e., the peptides may also bind to nontargets with high affinities. To this end, subtractive screening can be added to the basic biopanning steps. The subtractive strategy allows phages to interact with nontargets, and thus the unbound phages are candidates that are specific to the target of interest. For example, to identify the peptides that specifically bind to esophageal cancer cells, Zhang et al. use normal human esophageal epithelial cells as the nontarget to perform subtractive screening, followed by screening against esophageal cancer cells. They repeated this procedure for three rounds and discovered two peptides that exhibited higher binding affinities and specificities for the cancer cells, which were validated by enzyme-linked immunosorbent assays (ELISAs), immunofluorescence assays, and immunohistochemistry assays [6].
\n
Improvement of peptide library screening could be performed through small modifications. A stepwise reduction of elution buffer pH in the final round of biopanning reduces low affinity phages, thus effectively further enriching for high affinity phages. Optimized commercial kits are also available, for example, solid-phase screening, solution-sorting screening, kinetic antibody binding screening, and capture-sandwich ELISA screening [22, 23].
\n
\n
\n
2.2.3 In vivo screening
\n
In vivo screening of phage display is designed to isolate tissue-specific binders in living animals. Unlike in vitro screening, this in vivo approach considers the complexity and heterogeneity of the living organism and thus is one step closer to clinical applications. The phage library is administered directly into a living animal and allowed to circulate for a period of time, and then the animal is sacrificed with the desired organ extracted and homogenized in saline. The lysates or pelleted cells of the organ are used to infect E. coli so that the phages with high-affinity binding peptides are amplified. This procedure is repeated several rounds, and the resultant phages are sequenced to determine the binding peptide sequences. Similar to in vitro screening, in vivo screening can have a step to wash away unbound phages. It is achieved usually by perfusion of the left ventricle of the animal with saline [24].
\n
In vivo screening faces a more complicated environment than in vitro screening and thus requires extra considerations. Filamentous bacteriophages are often used for in vitro screening; however these viral particles are quite long (>500 nm) and thus may have problems during extravasation to some tissues. For example, M13 phage cannot be used to target liver parenchymal cells due to the impermeability problem [25]. Instead, T7 bacteriophage is used to identify peptides targeting livers because it is smaller in size. An even more challenging issue for in vivo phages is how to avoid immune surveillance for accurate phage displays. Host immune system, particularly reticuloendothelial system, degrades phages quickly and increases nonspecific uptake in the liver and spleen. As expected, the severity of these phenomena reduces within immune-compromised nude and SCID mouse strains. Glycosylation and succinylation to wild-type M13 phages substantially reduce its half-life in murine bloodstream from 4.5 hours to 18 and 1.5 minutes, respectively [26]. This indicates that phages modified to display peptides should have a similarly short half-life, which is consistent with existing data. Therefore, the optimal time of phage library circulation needs to be determined before the actual in vivo phage display experiments. The time varies with phage modifications and targeted tissues.
\n
Phage library administration is another concern for in vivo screening. Administration approaches determine circulation routes of phages in living animals. The most widely used approach is intravenous delivery. It enables rapid exposure of the phages to vascular receptors of any organ or tissue. However, this approach is inappropriate to the discovery of peptides targeting brain tissues due to the blood-brain barrier. To this end, Wan et al. administered phage library intranasally and identified a peptide targeting the brain, which performs 50-fold better than random control peptides. Other “bloodless” approaches including site-directed phage administrations and transdermal delivery have been used successfully to identify targeting peptides [27].
\n
\n
\n
\n
\n
3. General considerations for phage display to target membrane receptors
\n
Membrane proteins are the most popular targets for diagnostic and therapeutic applications. The structures of membrane proteins are generally composed of three parts, i.e., the extracellular, transmembrane, and intracellular domains. The extracellular domains are the primary targets of drug discovery and diagnosis. About 60% of drug targets are membrane proteins [28]. More specifically, membrane proteins are targeted by the 61% monoclonal antibodies approved or under review as therapeutic drugs throughout Europe and the United States. This prevalence is all attributed to the unique properties of membrane proteins. First, they have various important biological functions such as in signaling and cell channels; thus drugs targeting them can manipulate cellular functions effectively. Second, membrane proteins are presented on cell surface and thus are more accessible than cellular proteins. Some membrane proteins can define cell types. For example, various cluster of differentiation (CD) markers are membrane proteins and define immune cell types. More importantly, diseases usually alter expression levels of membrane proteins. A well-known example is the overexpression of human epidermal growth factor receptor 2 (HER2) membrane protein in 20-25% of breast cancers.
\n
Despite being popular targets, membrane proteins present a limitation for phage display. The key to a successful phage display is the presentation of correctly folded targets, i.e., native structures of extracellular domains (ectodomains) in membrane proteins. This is fairly easy for soluble proteins because they fold correctly in solution while being immobilized on a surface, whereas membrane proteins usually fail to fold into their native structure in solution without membranes [29]. For example, G protein-coupled receptors (GPCRs) constitute the largest class of drug targets but have had limited success in phage display due to their hydrophobic regions and complicated ectodomains, which are usually comprised of the N-terminal chain, parts of the seven transmembrane helices, and their connecting loops. To stabilize the membrane proteins, several methods have been developed. The principle of this method is to engineer the membrane proteins by mutations or adding hydrophilic domains so that they maintain stability in solution for phage display. Note that such engineering must not interfere with the native fold of the ectodomain of membrane proteins.
\n
Another way to circumvent the limitation of unstable membrane proteins in solution is directly biopanning on whole cells instead of immobilizing membrane proteins on a surface as targets for phage display screening. Although this whole cell panning provides membrane proteins in native state as screening targets, it causes extra difficulties. First, the membrane protein may be present at low density on the cell surface; thus other nontargeted membrane proteins generate a high background noise. Second, other components on the surface of cells, such as sugar or lipid polymers, may sequester phage particles for nonspecific uptake into a cell. Taken together, both of these possibilities facilitate the selection of nonspecific ligands, rendering phage display inefficient. To address these newly introduced problems, Jones et al. have reported a modified phage display screening for antibodies. The key innovation is that the cell is transfected so that the target membrane protein and green fluorescent protein (GFP) are highly expressed simultaneously. For phage display, the green fluorescence provides a means to select only the cells with the target membrane protein highly expressed on cell surface using fluorescence-activated cell sorting (FACS) [29]. In other steps of phage display, small but nontrivial modifications are also adopted to improve or overcome the problems of using whole cells. For example, a low pH wash is found effective in removing phage that is present through nonantibody binding. Details of these many small modifications in phage display protocols are reviewed by Alfaleh et al. [30].
\n
A third category of methods has also been developed to create cell membrane-like microenvironments that preserve the stability and integrity of membrane proteins for phage display. In the first method, the membrane protein is purified in the presence of detergents, which forms micelles after exceeding their critical micellar concentration. These micelles mimic cell membrane and have been used in phage display to identify antibodies to the sodium-citrate cotransporter and the fluoride ion channel. However, detergent micelles themselves are unstable and heterogeneous in size, which may cause membrane proteins to unfold or aggregate. In another method, the membrane protein is inserted into a liposome, which is a bilayer structure that more closely mimics the cell membrane than detergent micelles. Recently, nanodiscs and virus-like particles (VLP) have been developed to mimic host membrane protein. Nanodiscs are macromolecular structures that spontaneously assemble when lipids and apolipoprotein A1 or B are mixed. In general, one nanodisc structure contains a lipid bilayer of ~1000 phospholipids bundled by two apolipoproteins. The diameter of a nanodisc is ~10 nm and thus houses only one membrane protein approximately. Nanodiscs can take in a membrane protein through coupled in vitro transcription-translation. A VLP contains viral capsid proteins, lipids, and membrane proteins on its surface, but not a viral genome. It is much more stable than native cells, micelles, and liposomes and thus can withstand wash buffers with detergents, which decreases nonspecific binding in phage display.
\n
In summary, some simple ectodomains of membrane proteins can be directly immobilized on plastic surfaces and treated as soluble proteins in phage display, whereas some other membrane proteins need to be engineered to increase ectodomain stability and integrity before phage display. Various nanoparticles such as detergent micelle, nanodisc, and VLP have been developed to create membrane-like environments to house membrane proteins. Panning directly on wild-type cells or on engineered cells, e.g., with membrane proteins highly expressed, is another way to represent membrane proteins for phage display. Such methods have to manage high background noise from cells. However, these methods have a unique advantage, i.e., consistent with native binding mechanisms. Many membrane receptors, e.g., cytokine receptors, exert their biological functions through ligand binding and dimerization. The ligand may interact with the monomer first and then mediate dimerization for function or bind to the dimer directly and then carry out its function. These two scenarios may both occur depending on the ligand concentrations [31]. Therefore, in those methods without whole cells, the monomer immobilized in phage display may not mimic the targets in vivo, and thus the ligand selected by phage display may not bind to in vivo receptors with high affinities.
\n
\n
\n
4. Phage display provides potential therapeutic and diagnostic agents
\n
Peptide phage display has played an important role in the development of clinically useful therapeutics and diagnostic agents. Peptide-based therapeutics have attracted a significant level of interest in the drug discovery and development industry. First, phage particles themselves can be used as the therapeutic agent. For example, the M13 bacteriophage was used successfully to treat a bacterial infection by delivering DNA encoding for bactericidal toxin proteins [32].
\n
Second, peptides derived from phage display can be used as therapeutic drugs. In 2017, peptide drug annual market was approximately $300–500 million and is estimated to increase 25% each year [33]. Compared to proteins and antibodies, peptides have numerous advantages, for example, low manufacturing costs, better activity and stability, negligible immunogenicity, and superior organ penetration. A number of peptide drugs developed from phage display technique have been approved or are currently in clinical trials. For example, DX-890, an inhibitor of human neutrophil elastase, with potential application in the treatment of pulmonary diseases such as cystic fibrosis and chronic obstructive pulmonary disease, was originated from phage display [34]. Ecallantide, a highly potent inhibitor of human plasma kallikrein, has been approved by the US Food and Drug Administration for the treatment of acute hereditary angioedema [35].
\n
Filamentous phage has also been used as an immunogenic carrier useful in vaccine development, with high immunogenicity, low production cost, and high stability. In addition, phage can also act as a gene-delivery vehicle. For example, phage can deliver functional genes to mammalian cells through receptor-mediated endocytosis.
\n
Phage-derived peptides that bind protein targets with high affinity and specificity can be used as molecular imaging probes. The classic example is octreotide, an eight amino acid cyclized peptide that binds the somatostatin receptor. 111In-DTPA-octreotide (OctreoScan®) has been used successfully to image somatostatin receptor-positive tumors in humans [36].
\n
\n
\n
5. Applications of targeting peptides derived from phages in clinical imaging
\n
Targeted molecular imaging of disease processes, particularly tumor growth and metastasis, has been a focus of many investigations recently. Molecular imaging probes have assisted in the understanding of fundamental biological processes, disease pathologies, as well as pharmaceutical development. Enormous progress has been made in both discovery of imaging probes and development of imaging instruments. Additionally, optical imaging methods provide many advantages over other imaging modalities that include high sensitivity, the use of nonradioactive materials, and safe detection using readily available instruments at moderate cost. Today, in vivo imaging can be applied at preclinical and clinical settings due to significant improvements in engineering technologies, optical systems, and advanced imaging instruments. These technologies in a combination with cutting-edge optical imaging probes provide noninvasive, real-time imaging at macroscopic and cellular levels. Indeed, the combination of numerous NIR probes and targeted ligands, such as antibodies, aptamers, and engineered peptides, has significantly enhanced the performance of optical imaging systems. Recent progress in clinical imaging and the utilization of phage-derived targeting peptides are reviewed below.
\n
\n
5.1 Magnetic resonance imaging
\n
MRI is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body, including in healthy and diseased tissues and organs. MRI scanners use strong magnetic fields, electric field gradients, and radio waves to generate images of the organs in the body. After a radiofrequency pulse, MRI detects the relaxation times of magnetic dipoles, such as hydrogen atoms in water and organic compounds, and generates MR signals. MRI offers spatial resolution on the millimeter scale with simultaneous physiological and anatomical correlation. However, MRI requires long scan and postprocessing times and has relatively low sensitivity, thus requiring high doses of magnetic contrast agents.
\n
In a reparative or reactive process, excess fibrous connective tissue (type I collagen) or fibrosis could be formed in a tissue. This is a common consequence in many chronic heart, kidney, liver, lung, or vasculature diseases. The high levels of collagen in fibrosis make it an attractive MRI target. Therefore, a collagen-specific MRI contrast agent was developed. A type I collagen-specific peptide was identified using phage display and subsequently modified to improve affinity for collagen. Conjugate EP-3533 consists of a peptide of 16 amino acids, with 3 amino acids flanking a cyclic peptide of 10 amino acids that is formed through a disulfide bond. The peptide was modified with biphenylalanine and gadolinium to improve collagen binding and sensitivity. EP-3533 was evaluated in a mouse model of aged myocardial infarction. From MR images, EP-3533 was able to enhance the collagen-rich scar, providing specific, high-contrast images compared to adjacent viable myocardium tissues and blood vessels [37].
\n
Another example of the utilization of peptides from phage with MRI in early detection of colorectal cancer (CRC) was reported. Human gastric mucin (MUC5AC) is secreted in the colonic mucus of cancer patients. MUC5AC is a specific marker of precancerous lesions called aberrant crypt foci. MRI can detect the accumulation of MUC5AC in xenograft and mouse stomach. To enhance MRI visualization, peptides that specifically bound MUC5AC were developed using an M13 phage library. Once, the peptide binding MUC5AC (C-PSIYPLL-C, 60C) was identified; it was synthesized and conjugated to biotin and finally to ultra-small particles of iron oxide (USPIOs). The ability of USPIO-60C to detect MUC5AC in vivo was investigated on two xenograft mouse models. A heterogeneous but significant negative enhancement was observed in MUC5AC-secreting tumor postcontrast images 1 hour after intravenous USPIO-60C administration [38]. The results provided in this study supply a proof of concept that targeted contrast agents can be used to detect pathologies earlier than allowed by conventional MRI approaches or clinical assessment.
PET and SPECT are nuclear medicine tomographic imaging techniques using gamma (γ) rays. Both techniques require the injection of a radioactive tracer. There are three main tracers used in SPECT imaging: technetium-99m, iodine-123, and iodine-131. The radioactive tracer emits gamma rays from the patient. PET and SPECT record high- and low-energy γ-rays emitted from within the body. These imaging modalities have very high sensitivity but relatively low spatial resolution.
\n
VRPMPLQ (VQ) is a heptapeptide sequence first identified by Hsiung and colleagues by screening phage display peptide libraries against fresh human colonic adenomas [39]. In a later study, Shi and team synthesized and evaluated 99mTc-HYNIC-VQ (HYNIC 5,6-hydrazinonicotinamide) as a SPECT radiotracer for tumor imaging in five different xenograft mouse models (HT-29 human colon cancer, CL187 human colon cancer, BGC823 human gastric cancer, U87MG human glioma, and UM-SCC-22B human head and neck cancer). The images were acquired 1 and 2 hours postinjection. The tumors were clearly visualized at 1 hour postinjection with excellent target-to-background (T/B) contrast. The studies demonstrated that 99mTc-HYNIC-VQ could provide high-contrast images in different tumor models and an inflammation model [40].
\n
In another study, a radioactive probe targeted to a dysplastic lesion in inflammatory bowel disease (IBD) or early CRC was developed. The cyclic peptide c[Cys-Thr-Pro-Ser-Pro-Phe-Ser-His-Cys]OH (TCP-1) was originally identified in an orthotopic mouse CRC model using phage display selection [41]. TCP-1 peptide was labeled with radioisotope technetium-99 m (99mTc) and the NIR fluorophore cyanine-7 (Cy7) for molecular imaging. The in vivo images of 99mTc-TCP-1 in xenografted HCT116 and PC3 prostate cancer models were collected using dynamic or static SPECT. The 99mTc-TCP-1 or control peptides were administered via intravenous or tail vein injection. Dynamic images of 99mTc-TCP-1 in HCT116 colon cancer xenograft mice exhibited that the tumor could be detected in 15–30 minutes after injection and remained visible until 180 minutes. The data demonstrated the feasibility of TCP-1-targeted detection of colorectal tumor [42].
\n
\n
\n
5.3 Photoacoustic tomography
\n
Photoacoustic tomography (PAT) is an emerging imaging technique that demonstrates great potential for preclinical research and clinical applications. PAT is a hybrid system that detects the acoustic energy of endogenous chromophore or exogenous contrast agent optical absorption. PAT generates high-resolution images in both the optical ballistic and diffusive regimes due to less ultrasound scatter in tissue. Over the past decade, the photoacoustic technique has been developing rapidly, leading to exciting findings and applications.
\n
Epidermal growth factor receptor (EGFR) is highly overexpressed in hepatocellular carcinoma (HCC). Therefore, it is a potential cell surface molecule for in vivo targeted imaging of HCC. A peptide specific for EGFR previously reported by Zhou and team was conjugated to Cy5.5 dye. Nude mice were injected with EGFR overexpressed human HCC cells. A 2D ultrasound scanner and MRI system were used to monitor tumor growth in the mice. Cy5.5-labeled EGFR and control peptides were injected to the mice separately. Photoacoustic images were recorded periodically for 24 hours. At 3 hours postinjection, the maximum photoacoustic signal in tumors was seen and results in high-contrast images of tumors beneath the skin. The T/B ratio was significantly different between the EGFR and control peptide. The signal was diminished by 24 hours [43]. From the data, a peptide specific for EGFR can detect HCC xenograft tumors in vivo with photoacoustic imaging.
\n
\n
\n
5.4 Optical endomicroscopy
\n
Optical imaging offers several unique advantages. Optics is nonionizing and provides resolution on the micron scale. Another advantage of optical imaging is the ability to collect images in real time in comparison to other imaging modalities, such as MRI and PET.
\n
Endoscopes are thin, flexible instruments that provide a macroscopic view of the large mucosal surfaces in hollow organs internal to the human body. Endomicroscopy employs high numerical aperture (NA) optics to provide a small field-of-view (FOV) with micron-level resolution for observing subcellular features. It commonly requires scaling down the size of a conventional microscope design into a miniature package. Novel optical designs and scanning mechanisms have been developed to improve imaging performance for both endoscopy and endomicroscopy. These instruments provide a unique opportunity for early cancer detection and prevention by allowing biopsy or resection to be performed concurrently with diagnosis.
\n
\n
5.4.1 Wide-field fluorescence endoscopy
\n
Previously, all CRCs were believed to arise from adenomas that progress through the traditional adenocarcinoma sequence. Recently, this pathway has been found to account for approximately 60% of CRCs, and up to 35% are now attributed to the serrated pathway [44]. White-light endoscopy (WLE) that is normally used in colonoscopy is sensitive to gross morphologic abnormalities, such as polyps. Dysplasia that is flat in morphology, focal in size, and patchy in distribution appears “invisible” on conventional wide-field endoscopy. Therefore, imaging methods with improved contrast and sensitivity to molecular rather than morphological properties that could improve early detection and prevention of CRC are in needed. There are several reports on discovery and validation of targeted peptides derived from phage display for early detection of CRC [45].
\n
One group used phage display to identify a peptide that binds to dysplastic colonic mucosa in vivo in a genetically engineered mouse model of colorectal tumorigenesis, CPC;Apc [46, 47]. A peptide, QPIHPNNM, was isolated after several rounds of in vivo T7 library biopanning. The peptide was synthesized, fluorescently labeled, and purified. The peptide was sprayed topically in mouse distal colon. The wide-field fluorescent videos were recorded. After quantitative image analysis, the fluorescent-labeled peptide was significantly bound twofold greater to the colonic adenomas when compared to the control peptide. The target peptide also showed minimal binding to an activated KrasG12D mutant mouse model that demonstrates hyperplastic polyp-like features used as a control hyperplastic model that does not progress to carcinoma (Figure 3A) and the lumen of a CPC;Apc bred mouse negative (Figure 3B).
\n
Figure 3.
Images from wide-field endoscopy videos after topical application of fluorescence-labeled peptides. The top and bottom panels represent frames from white light and fluorescence, respectively. (A) The hyperplastic epithelium after QPI peptide application, (B) the lumen of a CPC;Apc bred mouse negative for Cre recombinase (control litter mate), (C) single adenoma after control peptide application, (D) single adenoma, and (E) multiple adenomas in a CPC;Apc mouse after QPI peptide application. Used with permission [47].
\n
c-Met overexpression has been shown to occur as an early event in colorectal adenocarcinoma. A peptide that has high affinity for the extracellular domain of human c-Met was discovered using an M-13 phage display library. GE-137 is a water-soluble cyclic peptide (AGSCYCSGPPRFECWCYETEGT) labeled with a cyanine dye with a high affinity for human c-Met. The quantitative biodistribution, pharmacokinetics, binding specificity, and qualitative fluorescence of GE-137 were assessed in a CRC xenograft mouse model using subcutaneous injection of the c-Met-expressing human CRC cell line HT29. Intravenously administered GE-137 accumulated in the c-Met-expressing tumor xenografts and left a fluorescent signal in the tumors and kidneys 120 and 240 minutes after injection (Figure 4). In a pilot study in 15 patients at high risk of colorectal neoplasia, a total of 101 lesions were detected during first inspection with white light (WL), and an additional 22 were detected during second inspection with dual WL/fluorescence (FL). After immunohistochemical analysis, 36 hyperplastic lesions and 8 serrated polyps were identified. Most of these were visible in fluorescent mode (94 and 100%, respectively), and the majority (78 and 87%, respectively) showed increased fluorescence. From the data, GE-137 peptide showed some specificity to hyperplasia and serrated lesions in CRC mouse model and patients [48].
\n
Figure 4.
WL and FL images of representative lesions. (a–c) The lesions that are visible in WL show increased fluorescence. (d) A lesion that is visible in WL has enhanced visibility in FL. (e, f) Flat lesions that were only visible in FL. Used with permission [48].
\n
Overexpression of EGFR has been reported in as high as 97% of colonic adenocarcinomas, and it is a validated biomarker for CRC. In one study, the extracellular domain of EGFR (EGFR-ECD) was expressed and purified [49]. A library of M13 bacteriophage was used to select peptide candidates that bind specifically to EGFR-ECD. A peptide, QRHKPRE, that is specific for EGFR was developed and validated. Peptide binding to cells occurred within 2.46 minutes and had an affinity of 50 nM. A NIR fluorescence endoscope was used to perform in vivo imaging to validate peptide binding to spontaneous colonic adenomas in a CPC;Apc mouse model via topical administration (Figure 5). T/B ratios of polyps and flat lesions were 4.0 ± 1.7 and 2.7 ± 0.7, respectively. Subsequently, specific peptide binding to human colonic adenomas was assessed on immunohistochemistry and immunofluorescence. On human colonic specimens, greater intensity from peptide binding to dysplasia than normal was found with a 19.4-fold difference.
\n
Figure 5.
In vivo imaging of colon in CPC;Apc mouse. (a) WL image of colon in CPC;Apc mouse shows the presence of polyp (arrow). (b) NIR fluorescence image after topical administration of QRH*-Cy5.5 shows increased intensity from polyp (arrow) and several flat lesions (arrowheads). (c) Image with Cy5.5-control peptide (PEH*-Cy5.5) shows minimal signal. (d) WL image shows no grossly visible lesions (polyps). (e) NIR fluorescence image with QRH*-Cy5.5 shows the presence of flat lesions (arrowheads). (f) Image with Cy5.5-control peptide shows minimal signal. Used with permission [49].
\n
In another study, a phage-derived peptide was tested for specific binding to sessile serrated adenomas (SSAs) in proximal colon which accounts for 35% in CRC. Joshi and team used phage display to identify a peptide that binds specifically to SSAs. Many SSA cells have the V600E mutation in BRAF. Therefore, peptide selection was performed with an M13 Ph.D.-7 phage display library using a biopanning strategy with subtractive hybridization with HT29 colorectal cancer cells containing the V600E mutation in BRAF [45]. Binding of fluorescently labeled peptide, KCCFPAQ , to colorectal cancer cells was evaluated with confocal fluorescence microscopy. The peptide showed an apparent dissociation constant of Kd = 72 nM and an apparent association time constant of K = 0.174/minute. Toxicity was also assessed in rats. In the clinical safety study, fluorescently labeled peptide was topically administered, using a spray catheter, to the proximal colon of 25 subjects undergoing routine outpatient colonoscopies. Subsequently, endoscopists resected identified lesions, which were analyzed histologically by gastrointestinal pathologists. Fluorescence intensities of SSAs were compared with those of normal colonic mucosa. During fluorescence imaging of patients during endoscopy, regions of SSA had 2.43-fold higher mean fluorescence intensity than that for normal colonic mucosa. Fluorescence labeling distinguished SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity.
\n
\n
\n
5.4.2 Confocal laser endomicroscopy
\n
Confocal laser endomicroscopy (CLE) is an endoscopic modality that based on tissue illumination using a low power laser and the subsequent detection of fluorescent light that is reflected back from the tissue through a pinhole. The term “confocal” refers to the alignment of both illumination and collection systems in the same plane. This alignment dramatically increases the spatial resolution of CLE and enables cellular imaging and evaluation of tissue architecture at the focal plane. CLE can be used to guide biopsies and has been demonstrated in a number of clinical studies to detect cancer in the digestive tract, bladder, cervix, ovary, oral cavity, and lungs. CLE requires the use of a fluorescent contrast agent to enhance visualization of cells. Contrast agents can be administered intravenously or topically. Intravenous fluorescein sodium and acriflavine are widely used contrast agents. CLE can be performed shortly following injection with its fluorescence lasting approximately 30 minutes. However, due to the lack of specificity of conventional contrast agents, there is an increasing use of tissue-specific binding molecular probes in CLE. The studies that used CLE in combination with a targeting peptide derived from phage display are summarized below.
\n
Hsiung et al. used an M13 phage library to identify peptides that would specifically bind dysplastic colonic mucosa from fresh human colonic biopsies [39]. A peptide (VRPMPLQ) that bound to colonic dysplasia was identified, synthesized, and conjugated with fluorescein for in vivo testing in a pilot study in patients undergoing routine colonoscopy using a flexible-fibered confocal microscope. Fluorescence images and videos of bound topically administered peptide collected in vivo showed that the selected peptide bound more strongly to dysplastic colonocytes than to the adjacent normal mucosa in the same subject with 81% sensitivity and 82% specificity.
\n
In another study, Qiu and team demonstrated vertical cross-sectional (XZ-plane) images of NIR fluorescence with a handheld dual-axis confocal endomicroscope that revealed a specific binding of a Cy5.5-labeled peptide (LTTHYKLGGGSK-Cy5.5) to premalignant colonic mucosa in mice [50]. This targeting peptide was selected using in vivo phage display technology in a CPC;Apc mouse model which developed adenomas spontaneously in the distal colon. NIR vertical cross-sectional fluorescence images of fresh mouse colonic mucosa demonstrate histology-like imaging performance as shown in Figure 6. The peptide showed specific binding and distinguished premalignant colonic mucosa from normal mucosa.
\n
Figure 6.
Vertical cross-sectional image of colonic dysplasia. (a) Chemical structure of LTTHYKL peptide with GGGSK linker and Cy5.5 fluorophore. (b) NIR fluorescence image from CPC; Apc mouse colon ex vivo shows vertically oriented dysplastic crypts. (c) The border between normal colonic mucosa and dysplasia shows increased contrast from specific binding of the LTT*-Cy5.5 peptide. (d) Corresponding histology (H&E), scale bar 200 μm. Used with permission [50].
\n
Gastric cancer vessels may have many differentiating characteristics compared to normal vessels. However, identification of gastric cancer vascular endothelial cells is difficult. Co-culture of gastric cancer cells and vascular endothelial cells was suggested to simulate gastric solid tumor mass. In a study, GEBP11, a nine amino acid vascular homing peptide, was screened and identified using Ph.D.C7C phage display peptide library kit panning against Co-HUVECS cells [51]. Liu et al. used FITC-GEBP11 to identify gastric cancer in mouse model [52]. A whole-body fluorescent imaging was first used to screen for the strongest specific fluorescent signal in xenograft models after tail vein injection of FITC-GEBP11. A specific signal was observed in both subcutaneous and orthotopic xenograft models in vivo, whereas the group injected with FITC-URP, a control peptide, showed no fluorescent signals. In addition, neoplastic and nonneoplastic gastric mucosae obtained from the patients were incubated with FITC-GEBP11 or FITC-URP for 30 minutes and were scanned with CLE. A specific signal of GEBP11 was observed in 26/28 neoplastic human specimens and in 8/28 samples of nonneoplastic specimens (p < 0.01).
\n
Sturm and team developed a peptide (ASYNYDA) that binds specifically to high-grade esophageal dysplasia and adenocarcinoma using phage display technology [53]. After peptide specific binding validation in human esophageal cancer specimens, they applied peptide topically and performed confocal endomicroscopy in 25 patients. The targeting peptide showed 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett’s esophagus and squamous epithelium with high sensitivity and specificity. The peptide revealed no toxicity in animals or patients.
\n
In a pilot study, Palma and team identified dysplasia lesions in ulcerative colitis (UC) patients using CLE and a fluorescently labeled peptide [54]. A phage-derived peptide (VRPMPLQ) was synthesized and conjugated with fluorescein. Eleven suspected dysplasia specimens were collected from nine UC patients. Specimens were stained with the peptide and subsequently inspected by CLE. The CLE images were correlated to histological results from specialists. The peptide showed a different pattern on dysplastic mucosa compared to nondysplastic lesions. However, due to several restrictions of this study, further studies on larger UC patients are required for systematic validation.
\n
ErbB2 expression in early breast cancer can predict tumor aggressiveness and clinical outcomes in patients. Up to 30% of all breast cancers express ErbB2, also known as HER2. Immunohistochemistry is commonly used to evaluate ErbB2 expression, but it has limitations due to tumor heterogeneity. Therefore, the use of a specific biomarker for ErbB2 is increasingly popular. One study used a NIR-labeled ErbB2 peptide and a handheld dual-axis CLE to detect in human xenograft breast tumors and human specimens [55]. As a result, they found significantly greater peptide binding to xenograft breast cancer in vivo and to human specimens of invasive ductal carcinoma that express ErbB2 ex vivo. From the data, a miniature dual-axis confocal fluorescence endomicroscope with ErbB2-specific peptide could be implemented to support future image-guided surgery.
\n
\n
\n
\n
5.5 Multimodality imaging
\n
Radiation-induced pulmonary fibrosis (RIPF) is a serious side effect of radiation therapy, especially in lung and breast cancers. Computed tomography (CT) imaging is currently utilized to identify and monitor RIPF. However, anatomical change interference is a major limitation of CT. Therefore, RIPF detection and observing techniques need to be improved. Collagen accumulation is common in fibrosis. In one study, a collagen-targeting peptide was fabricated to maximize the visualization of fibrosis using fluorescence endomicroscope imaging [37]. The probe showed moderate binding ability to collagen in a fibrosis in vitro binding assay and on lung tissue specimens. The probe showed a similar binding pattern on lung specimens compared to antibody. But its sensitivity was not as good as the collagen-binding antibody.
\n
In another study, Zhang and team evaluated the potential applicability of GEBP11 peptides in gastric cancer diagnosis and radiotherapy. They developed iodine 131-labeled GEBP11 peptides and derivatives [56]. The clinical potential of GEBP11 peptides was determined with multimodality imaging methods. Cerenkov and SPECT imaging showed significantly higher tumor uptake for 131I-2PEG-(GEBP11)3 trimer compared to monomer. Higher tumor accumulation and better T/B ratio of 131I-2PEG-(GEBP11)3 trimer were observed. Treating with 131I-2PEG-(GEBP11)3 trimer exhibited a significant tumor growth suppression compared to control and monomer groups. The tumor volume and vasculature decreased significantly after treatment with 131I-2PEG-(GEBP11)3 trimer, resulting in prolonged survival time. In addition, 131I-2PEG-(GEBP11)3 trimer showed no significant hepatic or renal toxicity. In conclusion, 131I-2PEG-(GEBP11)3 trimer could be a potential ligand used to identify gastric cancer and in antiangiogenic therapy.
\n
\n
\n
\n
6. Future prospects
\n
The discovery and development of therapeutic drugs and diagnostic probes are a time-consuming, expensive, and complex process. The processes involve experts from a wide range of disciplines such as medicinal chemistry, biochemistry, molecular biology, medicine, and pharmacology. It has been estimated that from about 10,000 new chemical entities identified, only one will reach the market in an average time of 16 years. Phage display, and particularly peptide phage display, has played a major role in the development pipeline for bringing peptide therapeutics into the clinic. Phage-derived peptides play an important role in disease detection and therapy, including in clinical imaging. The potential of peptides in preclinical and clinical molecular imaging is tremendous. Molecular imaging offers invaluable opportunities to explore complex disease-related biological processes at the molecular level in vivo. The emergence of current molecular imaging technologies is dependent not only on the progress of imaging systems but, more importantly, also on molecular imaging probes. Peptide-based imaging has now become an established approach in nuclear imaging, and its application is expanding to other imaging modalities. Considering the emergence of novel library designs and innovative selection strategies, we are confident that phage-derived peptides will continue to be promising biomarkers for early cancer detection, in metabolic abnormalities, and in personalized medicine.
\n
\n\n',keywords:"peptides, membrane receptors, imaging, phage display, endoscopy",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/66194.pdf",chapterXML:"https://mts.intechopen.com/source/xml/66194.xml",downloadPdfUrl:"/chapter/pdf-download/66194",previewPdfUrl:"/chapter/pdf-preview/66194",totalDownloads:602,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 7th 2018",dateReviewed:"January 9th 2019",datePrePublished:"March 18th 2019",datePublished:"February 19th 2020",dateFinished:null,readingETA:"0",abstract:"Phage display is a high-throughput technology used to identify peptides or proteins with high and specific binding affinities to a target, which is usually a protein biomarker or therapeutic receptor. In general, this technique allows peptides with a particular sequence to be presented on a phage particle. Peptides derived from phage display play an important role in drug discovery, drug delivery, cancer imaging, and treatment. Phage peptides themselves can act as sole therapeutics, for example, drugs, gene therapeutic, and immunotherapeutic agents that are comprehensively described elsewhere. In this chapter, we discuss phage selection and screening procedures in detail including some modifications to reduce nonspecific binding. In addition, the rationale for discovery and utilization of phage peptides as molecular imaging probes is focused upon. Molecular imaging is a new paradigm that uses advanced imaging instruments integrated with specific molecular imaging probes. Applications include monitoring of metabolic and molecular functions, therapeutic response, and drug efficacy, as well as early cancer detection, personalized medicine, and image-guided therapy.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/66194",risUrl:"/chapter/ris/66194",signatures:"Supang Khondee and Wibool Piyawattanametha",book:{id:"6910",title:"Bacteriophages",subtitle:"Perspectives and Future",fullTitle:"Bacteriophages - Perspectives and Future",slug:"bacteriophages-perspectives-and-future",publishedDate:"February 19th 2020",bookSignature:"Renos Savva",coverURL:"https://cdn.intechopen.com/books/images_new/6910.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"252160",title:"Dr.",name:"Renos",middleName:null,surname:"Savva",slug:"renos-savva",fullName:"Renos Savva"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"70846",title:"Dr.",name:"Wibool",middleName:null,surname:"Piyawattanametha",fullName:"Wibool Piyawattanametha",slug:"wibool-piyawattanametha",email:"wibool@gmail.com",position:null,institution:null},{id:"257847",title:"Dr.",name:"Supang",middleName:null,surname:"Khondee",fullName:"Supang Khondee",slug:"supang-khondee",email:"s.khondee@gmail.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Phage biology and phage selection screening methods",level:"1"},{id:"sec_2_2",title:"2.1 Phage biology",level:"2"},{id:"sec_3_2",title:"2.2 Phage selection screening methods",level:"2"},{id:"sec_3_3",title:"2.2.1 Peptide library",level:"3"},{id:"sec_4_3",title:"2.2.2 In vitro screening",level:"3"},{id:"sec_5_3",title:"2.2.3 In vivo screening",level:"3"},{id:"sec_8",title:"3. General considerations for phage display to target membrane receptors",level:"1"},{id:"sec_9",title:"4. Phage display provides potential therapeutic and diagnostic agents",level:"1"},{id:"sec_10",title:"5. Applications of targeting peptides derived from phages in clinical imaging",level:"1"},{id:"sec_10_2",title:"5.1 Magnetic resonance imaging",level:"2"},{id:"sec_11_2",title:"5.2 Positron emission tomography/single-photon emission computed tomography",level:"2"},{id:"sec_12_2",title:"5.3 Photoacoustic tomography",level:"2"},{id:"sec_13_2",title:"5.4 Optical endomicroscopy",level:"2"},{id:"sec_13_3",title:"5.4.1 Wide-field fluorescence endoscopy",level:"3"},{id:"sec_14_3",title:"5.4.2 Confocal laser endomicroscopy",level:"3"},{id:"sec_16_2",title:"5.5 Multimodality imaging",level:"2"},{id:"sec_18",title:"6. Future prospects",level:"1"}],chapterReferences:[{id:"B1",body:'Lee S, Xie J, Chen X. Peptide-based probes for targeted molecular imaging. Biochemistry. 2010;49(7):1364-1376\n'},{id:"B2",body:'De Jong M et al. Tumor imaging and therapy using radiolabeled somatostatin analogues. Accounts of Chemical Research. 2009;42(7):873-880\n'},{id:"B3",body:'Wu AM, Olafsen T. Antibodies for molecular imaging of cancer. The Cancer Journal. 2008;14(3):191-197\n'},{id:"B4",body:'Derda R et al. Diversity of phage-displayed libraries of peptides during panning and amplification. Molecules. 2011;16(2):1776-1803\n'},{id:"B5",body:'Smith GP. Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface. Science. 1985;228(4705):1315-1317\n'},{id:"B6",body:'Zhang ZF et al. Screening and selection of peptides specific for esophageal cancer cells from a phage display peptide library. Journal of Cardiothoracic Surgery. 2014;9(1):76\n'},{id:"B7",body:'Witt H et al. Identification of a rhabdomyosarcoma targeting peptide by phage display with sequence similarities to the tumour lymphatic-homing peptide LyP-1. International Journal of Cancer. 2009;124(9):2026-2032\n'},{id:"B8",body:'Hui X et al. Specific targeting of the vasculature of gastric cancer by a new tumor-homing peptide CGNSNPKSC. Journal of Controlled Release. 2008;131(2):86-93\n'},{id:"B9",body:'Wang W et al. Near-infrared optical imaging of integrin αvβ3 in human tumor xenografts. Molecular Imaging. 2004;3(4):15353500200404148\n'},{id:"B10",body:'Ye Y et al. Design, synthesis, and evaluation of near infrared fluorescent multimeric RGD peptides for targeting tumors. Journal of Medicinal Chemistry. 2006;49(7):2268-2275\n'},{id:"B11",body:'Comeau AM et al. Exploring the prokaryotic virosphere. Research in Microbiology. 2008;159(5):306-313\n'},{id:"B12",body:'Ofir G, Sorek R. Contemporary phage biology: From classic models to new insights. Cell. 2018;172(6):1260-1270\n'},{id:"B13",body:'Drulis-Kawa Z, Majkowska-Skrobek G, Maciejewska B. Bacteriophages and phage-derived proteins, application approaches. Current Medicinal Chemistry. 2015;22(14):1757-1773\n'},{id:"B14",body:'Murphy FA et al. Virus Taxonomy: Classification and Nomenclature of Viruses. Vol. 10. New York: Springer Science & Business Media; 2012\n'},{id:"B15",body:'Russel M, Lowman HB, Clackson T. Introduction to phage biology and phage display. In: Phage Display: A Practical Approach. New York: Oxford University Press; 2004. pp. 1-26\n'},{id:"B16",body:'Barbas CF, et al. Phage Display: A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press; 2001. pp. 1-24\n'},{id:"B17",body:'Pal G, Fellouse FA. Methods for the construction of phage-displayed libraries. In: Phage Display in Biotechnology and Drug Discovery. Florida: CRC Press; 2005. pp. 131-162\n'},{id:"B18",body:'Zeri AC et al. Structure of the coat protein in fd filamentous bacteriophage particles determined by solid-state NMR spectroscopy. Proceedings of the National Academy of Sciences. 2003;100(11):6458-6463\n'},{id:"B19",body:'Bratkovic T. Progress in phage display: Evolution of the technique and its applications. Cellular and Molecular Life Sciences. 2010;67(5):749-767\n'},{id:"B20",body:'Pande J, Szewczyk MM, Grover AK. Phage display: Concept, innovations, applications and future. Biotechnology Advances. 2010;28(6):849-858\n'},{id:"B21",body:'Hamzeh-Mivehroud M, Mahmoudpour A, Dastmalchi S. Identification of new peptide ligands for epidermal growth factor receptor using phage display and computationally modeling their mode of binding. Chemical Biology & Drug Design. 2012;79(3):246-259\n'},{id:"B22",body:'Matz J, Chames P. Phage display and selections on purified antigens. In: Antibody Engineering. Heidelberg: Springer; 2012. pp. 213-224\n'},{id:"B23",body:'Smolarek D, Bertrand O, Czerwinski M. Variable fragments of heavy chain antibodies (VHHs): A new magic bullet molecule of medicine? Advances in Hygiene & Experimental Medicine. 2012;66:348-358\n'},{id:"B24",body:'Kolonin MG et al. Synchronous selection of homing peptides for multiple tissues by in vivo phage display. The FASEB Journal. 2006;20(7):979-981\n'},{id:"B25",body:'Ludtke JJ et al. In vivo selection and validation of liver-specific ligands using a new T7 phage peptide display system. Drug Delivery. 2007;14(6):357-369\n'},{id:"B26",body:'Molenaar TJ et al. Uptake and processing of modified bacteriophage M13 in mice: Implications for phage display. Virology. 2002;293(1):182-191\n'},{id:"B27",body:'Wu M et al. Mapping alveolar binding sites in vivo using phage peptide libraries. Gene Therapy. 2003;10(17):1429\n'},{id:"B28",body:'Arinaminpathy Y et al. Computational analysis of membrane proteins: The largest class of drug targets. Drug Discovery Today. 2009;14(23-24):1130-1135\n'},{id:"B29",body:'Jones ML et al. Targeting membrane proteins for antibody discovery using phage display. Scientific Reports. 2016;6:26240\n'},{id:"B30",body:'Alfaleh MA et al. Strategies for selecting membrane protein-specific antibodies using phage display with cell-based panning. Antibodies. 2017;6(3):10\n'},{id:"B31",body:'Schooltink H, Rose-John S. Designing cytokine variants by phage-display. Combinatorial Chemistry & High Throughput Screening. 2005;8(2):173-179\n'},{id:"B32",body:'Westwater C et al. Use of genetically engineered phage to deliver antimicrobial agents to bacteria: An alternative therapy for treatment of bacterial infections. Antimicrobial Agents and Chemotherapy. 2003;47(4):1301-1307\n'},{id:"B33",body:'Lau JL, Dunn MK. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorganic & Medicinal Chemistry. 2017;26:2700-2707\n'},{id:"B34",body:'Rothe A, Hosse RJ, Power BE. In vitro display technologies reveal novel biopharmaceutics. The FASEB Journal. 2006;20(10):1599-1610\n'},{id:"B35",body:'Zuraw, B, Yasothan U, Kirkpatrick P. Ecallantide. Nature Reviews Drug Discovery. 2010;9:189-190\n'},{id:"B36",body:'Froidevaux S, Eberle AN. Somatostatin analogs and radiopeptides in cancer therapy. Peptide Science. 2002;66(3):161-183\n'},{id:"B37",body:'Caravan P et al. Collagen-targeted MRI contrast agent for molecular imaging of fibrosis. Angewandte Chemie International Edition. 2007;46(43):8171-8173\n'},{id:"B38",body:'Rossez Y et al. Early detection of colonic dysplasia by magnetic resonance molecular imaging with a contrast agent raised against the colon cancer marker MUC5AC. Contrast Media & Molecular Imaging. 2016;11(3):211-221\n'},{id:"B39",body:'Hsiung PL et al. Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nature Medicine. 2008;14(4):454\n'},{id:"B40",body:'Shi J et al. Technetium 99m–labeled VQ peptide: A new imaging agent for the early detection of tumors or premalignancies. Molecular Imaging. 2013;12(5):7290.2012. 00047\n'},{id:"B41",body:'Li ZJ et al. A novel peptide specifically targeting the vasculature of orthotopic colorectal cancer for imaging detection and drug delivery. Journal of Controlled Release. 2010;148(3):292-302\n'},{id:"B42",body:'Liu Z et al. Characterization of TCP-1 probes for molecular imaging of colon cancer. Journal of Controlled Release. 2016;239:223-230\n'},{id:"B43",body:'Zhou Q et al. In vivo photoacoustic tomography of EGFR overexpressed in hepatocellular carcinoma mouse xenograft. Photoacoustics. 2016;4(2):43-54\n'},{id:"B44",body:'Snover DC. Update on the serrated pathway to colorectal carcinoma. Human Pathology. 2011;42(1):1-10\n'},{id:"B45",body:'Joshi BP et al. Detection of sessile serrated adenomas in the proximal colon using wide-field fluorescence endoscopy. Gastroenterology. 2017;152(5):1002-1013. e9\n'},{id:"B46",body:'Elahi SF et al. Targeted imaging of colorectal dysplasia in living mice with fluorescence microendoscopy. Biomedical Optics Express. 2011;2(4):981-986\n'},{id:"B47",body:'Miller SJ et al. In vivo fluorescence-based endoscopic detection of colon dysplasia in the mouse using a novel peptide probe. PLoS One. 2011;6(3):e17384\n'},{id:"B48",body:'Burggraaf J et al. Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nature Medicine. 2015;21(8):955\n'},{id:"B49",body:'Zhou J et al. EGFR overexpressed in colonic neoplasia can be detected on wide-field endoscopic imaging. Clinical and Translational Gastroenterology. 2015;6(7):e101\n'},{id:"B50",body:'Qiu Z et al. Targeted vertical cross-sectional imaging with handheld near-infrared dual axes confocal fluorescence endomicroscope. Biomedical Optics Express. 2013;4(2):322-330\n'},{id:"B51",body:'Liang S et al. Screening and identification of vascular-endothelial-cell-specific binding peptide in gastric cancer. Journal of Molecular Medicine. 2006;84(9):764-773\n'},{id:"B52",body:'Liu L et al. In vivo molecular imaging of gastric cancer in human-murine xenograft models with confocal laser endomicroscopy using a tumor vascular homing peptide. Cancer Letters. 2015;356(2):891-898\n'},{id:"B53",body:'Sturm MB et al. Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: First-in-human results. Science Translational Medicine. 2013;5(184):184ra61-184ra61\n'},{id:"B54",body:'De Palma GD et al. Detection of colonic dysplasia in patients with ulcerative colitis using a targeted fluorescent peptide and confocal laser endomicroscopy: A pilot study. PLoS One. 2017;12(6):e018050e9\n'},{id:"B55",body:'Gao Z et al. In vivo near-infrared imaging of ErbB2 expressing breast tumors with dual-axes confocal endomicroscopy using a targeted peptide. Scientific Reports. 2017;7(1):14404\n'},{id:"B56",body:'Zhang J et al. Targeted radiotherapy with tumor vascular homing trimeric GEBP11 peptide evaluated by multimodality imaging for gastric cancer. Journal of Controlled Release. 2013;172(1):322-329\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Supang Khondee",address:null,affiliation:'
School of Pharmaceutical Sciences, University of Phayao, Thailand
Faculty of Engineering, Department of Biomedical Engineering, King Mongkut’s Institute of Technology Ladkrabang (KMITL), Thailand
Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, USA
'}],corrections:null},book:{id:"6910",title:"Bacteriophages",subtitle:"Perspectives and Future",fullTitle:"Bacteriophages - Perspectives and Future",slug:"bacteriophages-perspectives-and-future",publishedDate:"February 19th 2020",bookSignature:"Renos Savva",coverURL:"https://cdn.intechopen.com/books/images_new/6910.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"252160",title:"Dr.",name:"Renos",middleName:null,surname:"Savva",slug:"renos-savva",fullName:"Renos Savva"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"183268",title:"Prof.",name:"Wendy",middleName:null,surname:"Meulebroeck",email:"wmeulebr@b-phot.org",fullName:"Wendy Meulebroeck",slug:"wendy-meulebroeck",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{title:"Improving Food Safety by Using One- and Two-Photon- Induced Fluorescence Spectroscopy for the Detection of Mycotoxins",slug:"improving-food-safety-by-using-one-and-two-photon-induced-fluorescence-spectroscopy-for-the-detectio",abstract:"The presence of mycotoxins in food products is a major worldwide problem. Nowadays, mycotoxins can only be detected by the use of sample-based chemical analyses. Therefore, we demonstrate the use of one- and two-photon-induced fluorescence spectroscopy for the non-destructive detection of mycotoxins in unprocessed food products. We first explain our optical set-up, which is able to measure the localized one- and two-photon-induced fluorescence spectra. Following, as a case study, the detection of aflatoxin in maize kernels is discussed. We present our research methodology, from the characterization of the fluorescence of pure aflatoxin, to the study of the one- and two- photon-induced fluorescence spectra of maize kernels and the development of an optical detection criterion. During both one- and two-photon-induced fluorescence processes, the fluorescence of the aflatoxin influences the intrinsic fluorescence of the maize. Based on the fluorescence spectrum between 400 and 550 nm, a detection criterion to sense the contaminated kernels is defined. Furthermore, we successfully monitored the localized contamination level on the kernel’s surface, showing both contaminated kernels with a high contamination in a limited surface area (a few square millimetres) and kernels with a low contamination spread over a large surface area (up to 20 mm2). Finally, the extensibility of our research methodology to other fluorescent mycotoxins is discussed.",signatures:"Lien Smeesters, Wendy Meulebroeck and Hugo Thienpont",authors:[{id:"182428",title:"Ph.D.",name:"Lien",surname:"Smeesters",fullName:"Lien Smeesters",slug:"lien-smeesters",email:"lsmeeste@b-phot.org"},{id:"183268",title:"Prof.",name:"Wendy",surname:"Meulebroeck",fullName:"Wendy Meulebroeck",slug:"wendy-meulebroeck",email:"wmeulebr@b-phot.org"},{id:"183270",title:"Prof.",name:"Hugo",surname:"Thienpont",fullName:"Hugo Thienpont",slug:"hugo-thienpont",email:"hthienpo@b-phot.org"}],book:{title:"Applications of Molecular Spectroscopy to Current Research in the Chemical and Biological Sciences",slug:"applications-of-molecular-spectroscopy-to-current-research-in-the-chemical-and-biological-sciences",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"55520",title:"Prof.",name:"Ping",surname:"Chen",slug:"ping-chen",fullName:"Ping Chen",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"61965",title:"Prof.",name:"Lie",surname:"Lin",slug:"lie-lin",fullName:"Lie Lin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"181863",title:"Dr.",name:"Andrzej",surname:"Łapiński",slug:"andrzej-lapinski",fullName:"Andrzej Łapiński",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Polish Academy of Sciences",institutionURL:null,country:{name:"Poland"}}},{id:"183048",title:"Dr.",name:"Philip",surname:"Westergaard",slug:"philip-westergaard",fullName:"Philip Westergaard",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"183253",title:"Associate Prof.",name:"Jana",surname:"Sádecká",slug:"jana-sadecka",fullName:"Jana Sádecká",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Slovak University of Technology in Bratislava",institutionURL:null,country:{name:"Slovakia"}}},{id:"183261",title:"Prof.",name:"Miroslav",surname:"Dramicanin",slug:"miroslav-dramicanin",fullName:"Miroslav Dramicanin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Belgrade",institutionURL:null,country:{name:"Serbia"}}},{id:"183280",title:"Dr.",name:"Tatjana",surname:"Dramicanin",slug:"tatjana-dramicanin",fullName:"Tatjana Dramicanin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"183365",title:"Dr.",name:"Lu",surname:"Sun",slug:"lu-sun",fullName:"Lu Sun",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"183378",title:"Dr.",name:"Michaela",surname:"Jakubíková",slug:"michaela-jakubikova",fullName:"Michaela Jakubíková",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"183379",title:"Dr.",name:"Veronika",surname:"Uríčková",slug:"veronika-urickova",fullName:"Veronika Uríčková",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"open-access-funding-funders-list",title:"List of Funders by Country",intro:"
If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
IMPORTANT: You must be a member or grantee of the listed funders in order to apply for their Open Access publication funds. Do not attempt to contact the funders if this is not the case.
",metaTitle:"List of Funders by Country",metaDescription:"If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).",metaKeywords:null,canonicalURL:"/page/open-access-funding-funders-list",contentRaw:'[{"type":"htmlEditorComponent","content":"
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
\n
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5766},{group:"region",caption:"Middle and South America",value:2,count:5228},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10370},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15790}],offset:12,limit:12,total:118192},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateendthirdsteppublish"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:16},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:4},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:8},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:16},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:24},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:2},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[],offset:0,limit:12,total:null},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"158",title:"Metals and Nonmetals",slug:"metals-and-nonmetals",parent:{title:"Materials Science",slug:"materials-science"},numberOfBooks:113,numberOfAuthorsAndEditors:2715,numberOfWosCitations:4307,numberOfCrossrefCitations:2028,numberOfDimensionsCitations:4622,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"metals-and-nonmetals",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editedByType:"Edited by",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8787",title:"Bismuth",subtitle:"Fundamentals and Optoelectronic Applications",isOpenForSubmission:!1,hash:"7751170d0b538f61d14a27a56e6567a5",slug:"bismuth-fundamentals-and-optoelectronic-applications",bookSignature:"Yanhua Luo, Jianxiang Wen and Jianzhong Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/8787.jpg",editedByType:"Edited by",editors:[{id:"226148",title:"Dr.",name:"Yanhua",middleName:null,surname:"Luo",slug:"yanhua-luo",fullName:"Yanhua Luo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9949",title:"Lead Chemistry",subtitle:null,isOpenForSubmission:!1,hash:"b2f999b9583c748f957f612227976570",slug:"lead-chemistry",bookSignature:"Pipat Chooto",coverURL:"https://cdn.intechopen.com/books/images_new/9949.jpg",editedByType:"Edited by",editors:[{id:"197984",title:"Ph.D.",name:"Pipat",middleName:null,surname:"Chooto",slug:"pipat-chooto",fullName:"Pipat Chooto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9190",title:"Stability and Applications of Coordination Compounds",subtitle:null,isOpenForSubmission:!1,hash:"3f07c532e478beb8fcd2fe53b8c9bcfd",slug:"stability-and-applications-of-coordination-compounds",bookSignature:"Abhay Nanda Srivastva",coverURL:"https://cdn.intechopen.com/books/images_new/9190.jpg",editedByType:"Edited by",editors:[{id:"293623",title:"Dr.",name:"Abhay Nanda",middleName:"Nanda",surname:"Srivastva",slug:"abhay-nanda-srivastva",fullName:"Abhay Nanda Srivastva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7787",title:"Rare Earth Elements and Their Minerals",subtitle:null,isOpenForSubmission:!1,hash:"7ba4060b0830f7a68f00557da8ed8a39",slug:"rare-earth-elements-and-their-minerals",bookSignature:"Michael Aide and Takahito Nakajima",coverURL:"https://cdn.intechopen.com/books/images_new/7787.jpg",editedByType:"Edited by",editors:[{id:"185895",title:"Dr.",name:"Michael",middleName:"Thomas",surname:"Aide",slug:"michael-aide",fullName:"Michael Aide"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7722",title:"Recent Advancements in the Metallurgical Engineering and Electrodeposition",subtitle:null,isOpenForSubmission:!1,hash:"0d7ff67bd6f4c13830658bc6f9a75851",slug:"recent-advancements-in-the-metallurgical-engineering-and-electrodeposition",bookSignature:"Uday Basheer Al-Naib, Dhanasekaran Vikraman and K. Karuppasamy",coverURL:"https://cdn.intechopen.com/books/images_new/7722.jpg",editedByType:"Edited by",editors:[{id:"182041",title:null,name:"Uday",middleName:"M.",surname:"Basheer Al-Naib",slug:"uday-basheer-al-naib",fullName:"Uday Basheer Al-Naib"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7775",title:"Metallic Glasses",subtitle:null,isOpenForSubmission:!1,hash:"665fb007e1e410d119fc09d709c41cc3",slug:"metallic-glasses",bookSignature:"Dragica Minić and Milica Vasić",coverURL:"https://cdn.intechopen.com/books/images_new/7775.jpg",editedByType:"Edited by",editors:[{id:"30470",title:"Prof.",name:"Dragica",middleName:"M",surname:"Minić",slug:"dragica-minic",fullName:"Dragica Minić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8653",title:"Electromagnetic Materials and Devices",subtitle:null,isOpenForSubmission:!1,hash:"0cc0489a203ae888b1105719a4e70ecd",slug:"electromagnetic-materials-and-devices",bookSignature:"Man-Gui Han",coverURL:"https://cdn.intechopen.com/books/images_new/8653.jpg",editedByType:"Edited by",editors:[{id:"250649",title:"Prof.",name:"Man-Gui",middleName:null,surname:"Han",slug:"man-gui-han",fullName:"Man-Gui Han"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8886",title:"Cobalt Compounds and Applications",subtitle:null,isOpenForSubmission:!1,hash:"0241f740fc6e17cd9dc69362ef388d04",slug:"cobalt-compounds-and-applications",bookSignature:"Yasemin Yıldız and Aynur Manzak",coverURL:"https://cdn.intechopen.com/books/images_new/8886.jpg",editedByType:"Edited by",editors:[{id:"208129",title:"Dr.",name:"Yasemin",middleName:null,surname:"Yıldız",slug:"yasemin-yildiz",fullName:"Yasemin Yıldız"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8416",title:"Non-Equilibrium Particle Dynamics",subtitle:null,isOpenForSubmission:!1,hash:"2c3add7639dcd1cb442cb4313ea64e3a",slug:"non-equilibrium-particle-dynamics",bookSignature:"Albert S. Kim",coverURL:"https://cdn.intechopen.com/books/images_new/8416.jpg",editedByType:"Edited by",editors:[{id:"21045",title:"Prof.",name:"Albert S.",middleName:null,surname:"Kim",slug:"albert-s.-kim",fullName:"Albert S. Kim"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8408",title:"Titanium Alloys",subtitle:"Novel Aspects of Their Manufacturing and Processing",isOpenForSubmission:!1,hash:"e5533136b732dc4ada818553023d4d55",slug:"titanium-alloys-novel-aspects-of-their-manufacturing-and-processing",bookSignature:"Maciej Motyka, Waldemar Ziaja and Jan Sieniawsk",coverURL:"https://cdn.intechopen.com/books/images_new/8408.jpg",editedByType:"Edited by",editors:[{id:"101690",title:"Associate Prof.",name:"Maciej",middleName:null,surname:"Motyka",slug:"maciej-motyka",fullName:"Maciej Motyka"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:113,mostCitedChapters:[{id:"37067",doi:"10.5772/35482",title:"Fourier Transform Infrared Spectroscopy for Natural Fibres",slug:"fourier-transform-infrared-spectroscopy-for-natural-fibres",totalDownloads:8295,totalCrossrefCites:119,totalDimensionsCites:287,book:{slug:"fourier-transform-materials-analysis",title:"Fourier Transform",fullTitle:"Fourier Transform - Materials Analysis"},signatures:"Mizi Fan, Dasong Dai and Biao Huang",authors:[{id:"104647",title:"Prof.",name:"Mizi",middleName:null,surname:"Fan",slug:"mizi-fan",fullName:"Mizi Fan"}]},{id:"60680",doi:"10.5772/intechopen.76082",title:"Environmental Contamination by Heavy Metals",slug:"environmental-contamination-by-heavy-metals",totalDownloads:12323,totalCrossrefCites:68,totalDimensionsCites:118,book:{slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]},{id:"46243",doi:"10.5772/57255",title:"Corrosion Inhibitors – Principles, Mechanisms and Applications",slug:"corrosion-inhibitors-principles-mechanisms-and-applications",totalDownloads:13006,totalCrossrefCites:30,totalDimensionsCites:105,book:{slug:"developments-in-corrosion-protection",title:"Developments in Corrosion Protection",fullTitle:"Developments in Corrosion Protection"},signatures:"Camila G. Dariva and Alexandre F. Galio",authors:[{id:"169261",title:"Dr.",name:"Camila",middleName:"G.",surname:"Dariva",slug:"camila-dariva",fullName:"Camila Dariva"},{id:"170138",title:"Dr.",name:"Alexandre",middleName:"Ferreira",surname:"Galio",slug:"alexandre-galio",fullName:"Alexandre Galio"}]}],mostDownloadedChaptersLast30Days:[{id:"60680",title:"Environmental Contamination by Heavy Metals",slug:"environmental-contamination-by-heavy-metals",totalDownloads:12290,totalCrossrefCites:66,totalDimensionsCites:115,book:{slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]},{id:"59905",title:"Synthesis of Silver Nanoparticles",slug:"synthesis-of-silver-nanoparticles",totalDownloads:5054,totalCrossrefCites:2,totalDimensionsCites:6,book:{slug:"silver-nanoparticles-fabrication-characterization-and-applications",title:"Silver Nanoparticles",fullTitle:"Silver Nanoparticles - Fabrication, Characterization and Applications"},signatures:"Remziye Güzel and Gülbahar Erdal",authors:[{id:"226613",title:"Dr.",name:"Remziye",middleName:null,surname:"Güzel",slug:"remziye-guzel",fullName:"Remziye Güzel"},{id:"240772",title:"MSc.",name:"Gülbahar",middleName:null,surname:"Erdal",slug:"gulbahar-erdal",fullName:"Gülbahar Erdal"}]},{id:"59857",title:"Introductory Chapter: Introducing Heavy Metals",slug:"introductory-chapter-introducing-heavy-metals",totalDownloads:4331,totalCrossrefCites:3,totalDimensionsCites:9,book:{slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Martin Koller and Hosam M. Saleh",authors:[{id:"144691",title:"Prof.",name:"Hosam",middleName:"M.",surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh"}]},{id:"60518",title:"Synthetic Methods for Titanium Dioxide Nanoparticles: A Review",slug:"synthetic-methods-for-titanium-dioxide-nanoparticles-a-review",totalDownloads:3286,totalCrossrefCites:10,totalDimensionsCites:17,book:{slug:"titanium-dioxide-material-for-a-sustainable-environment",title:"Titanium Dioxide",fullTitle:"Titanium Dioxide - Material for a Sustainable Environment"},signatures:"Pardon Nyamukamba, Omobola Okoh, Henry Mungondori,\nRaymond Taziwa and Simcelile Zinya",authors:[{id:"196100",title:"Dr.",name:"Raymond",middleName:null,surname:"Taziwa",slug:"raymond-taziwa",fullName:"Raymond Taziwa"},{id:"219920",title:"Prof.",name:"Omobola",middleName:null,surname:"Okoh",slug:"omobola-okoh",fullName:"Omobola Okoh"},{id:"226567",title:"Dr.",name:"Pardon",middleName:null,surname:"Nyamukamba",slug:"pardon-nyamukamba",fullName:"Pardon Nyamukamba"},{id:"239758",title:"Mr.",name:"Simcelile",middleName:null,surname:"Zinya",slug:"simcelile-zinya",fullName:"Simcelile Zinya"}]},{id:"58868",title:"Iron Ore Pelletizing Process: An Overview",slug:"iron-ore-pelletizing-process-an-overview",totalDownloads:3186,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"iron-ores-and-iron-oxide-materials",title:"Iron Ores and Iron Oxide Materials",fullTitle:"Iron Ores and Iron Oxide Materials"},signatures:"Sandra Lúcia de Moraes, José Renato Baptista de Lima and Tiago\nRamos Ribeiro",authors:[{id:"216788",title:"Dr.",name:"Sandra",middleName:"Lúcia",surname:"De Moraes",slug:"sandra-de-moraes",fullName:"Sandra De Moraes"},{id:"233466",title:"Prof.",name:"José Renato Baptista",middleName:null,surname:"De Lima",slug:"jose-renato-baptista-de-lima",fullName:"José Renato Baptista De Lima"},{id:"233467",title:"MSc.",name:"Tiago Ramos",middleName:null,surname:"Ribeiro",slug:"tiago-ramos-ribeiro",fullName:"Tiago Ramos Ribeiro"}]},{id:"58797",title:"Green Corrosion Inhibitors, Past, Present, and Future",slug:"green-corrosion-inhibitors-past-present-and-future",totalDownloads:2788,totalCrossrefCites:5,totalDimensionsCites:7,book:{slug:"corrosion-inhibitors-principles-and-recent-applications",title:"Corrosion Inhibitors, Principles and Recent Applications",fullTitle:"Corrosion Inhibitors, Principles and Recent Applications"},signatures:"Omnia S. Shehata, Lobna A. Korshed and Adel Attia",authors:[{id:"220734",title:"Associate Prof.",name:"Omnia",middleName:null,surname:"Shehata",slug:"omnia-shehata",fullName:"Omnia Shehata"},{id:"227918",title:"Prof.",name:"Adel",middleName:null,surname:"Attia",slug:"adel-attia",fullName:"Adel Attia"},{id:"227919",title:"Dr.",name:"Lobna",middleName:null,surname:"Korshed",slug:"lobna-korshed",fullName:"Lobna Korshed"}]},{id:"51497",title:"The Review of Some Commonly Used Methods and Techniques to Measure the Thermal Conductivity of Insulation Materials",slug:"the-review-of-some-commonly-used-methods-and-techniques-to-measure-the-thermal-conductivity-of-insul",totalDownloads:4196,totalCrossrefCites:13,totalDimensionsCites:28,book:{slug:"insulation-materials-in-context-of-sustainability",title:"Insulation Materials in Context of Sustainability",fullTitle:"Insulation Materials in Context of Sustainability"},signatures:"Numan Yüksel",authors:[{id:"178245",title:"Dr.",name:"Numan",middleName:null,surname:"Yüksel",slug:"numan-yuksel",fullName:"Numan Yüksel"}]},{id:"70661",title:"Bioremediation Techniques for Polluted Environment: Concept, Advantages, Limitations, and Prospects",slug:"bioremediation-techniques-for-polluted-environment-concept-advantages-limitations-and-prospects",totalDownloads:195,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",title:"Trace Metals in the Environment",fullTitle:"Trace Metals in the Environment - New Approaches and Recent Advances"},signatures:"Indu Sharma",authors:[{id:"301262",title:"Associate Prof.",name:"Indu",middleName:null,surname:"Sharma",slug:"indu-sharma",fullName:"Indu Sharma"}]},{id:"47427",title:"Corrosion and Surface Treatment of Magnesium Alloys",slug:"corrosion-and-surface-treatment-of-magnesium-alloys",totalDownloads:3470,totalCrossrefCites:10,totalDimensionsCites:24,book:{slug:"magnesium-alloys-properties-in-solid-and-liquid-states",title:"Magnesium Alloys",fullTitle:"Magnesium Alloys - Properties in Solid and Liquid States"},signatures:"Henry Hu, Xueyuan Nie and Yueyu Ma",authors:[{id:"170745",title:"Prof.",name:"Henry",middleName:null,surname:"Hu",slug:"henry-hu",fullName:"Henry Hu"}]},{id:"58695",title:"Organic Corrosion Inhibitors",slug:"organic-corrosion-inhibitors",totalDownloads:3133,totalCrossrefCites:4,totalDimensionsCites:13,book:{slug:"corrosion-inhibitors-principles-and-recent-applications",title:"Corrosion Inhibitors, Principles and Recent Applications",fullTitle:"Corrosion Inhibitors, Principles and Recent Applications"},signatures:"Bogumił Eugeniusz Brycki, Iwona H. Kowalczyk, Adrianna Szulc,\nOlga Kaczerewska and Marta Pakiet",authors:[{id:"197271",title:"Prof.",name:"Bogumil E.",middleName:null,surname:"Brycki",slug:"bogumil-e.-brycki",fullName:"Bogumil E. Brycki"},{id:"207547",title:"Dr.",name:"Iwona",middleName:null,surname:"Kowalczyk",slug:"iwona-kowalczyk",fullName:"Iwona Kowalczyk"},{id:"207548",title:"Dr.",name:"Adrianna",middleName:null,surname:"Szulc",slug:"adrianna-szulc",fullName:"Adrianna Szulc"},{id:"207549",title:"Dr.",name:"Olga",middleName:null,surname:"Kaczerewska",slug:"olga-kaczerewska",fullName:"Olga Kaczerewska"},{id:"220728",title:"MSc.",name:"Marta",middleName:null,surname:"Pakiet",slug:"marta-pakiet",fullName:"Marta Pakiet"}]}],onlineFirstChaptersFilter:{topicSlug:"metals-and-nonmetals",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/183268/wendy-meulebroeck",hash:"",query:{},params:{id:"183268",slug:"wendy-meulebroeck"},fullPath:"/profiles/183268/wendy-meulebroeck",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()