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ConceptsandApplications Thispageintentionallyleftblank
Nanotechnology inModernAnimal Biotechnology ConceptsandApplications Editedby
PAWANKUMARMAURYA,PHD
AssociateProfessor
DepartmentofBiochemistry
CentralUniversityofHaryana Mahendergarh,India
SANJAYSINGH,PHD
AssociateProfessor
DivisionofBiologicalandLifeSciences
SchoolofArtsandSciences
CentralCampus,AhmedabadUniversity Ahmedabad,Gujarat,India
NANOTECHNOLOGYINMODERNANIMALBIOTECHNOLOGYISBN:978-0-12-818823-1 Copyright 2019ElsevierInc.Allrightsreserved.
Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicor mechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem,without permissioninwritingfromthepublisher.Detailsonhowtoseekpermission,furtherinformationaboutthe Publisher’spermissionspoliciesandourarrangementswithorganizationssuchastheCopyrightClearance CenterandtheCopyrightLicensingAgency,canbefoundatourwebsite: www.elsevier.com/permissions
ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher (otherthanasmaybenotedherein).
Notices Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingand usinganyinformation,methods,compoundsorexperimentsdescribedherein.Becauseofrapidadvances inthemedicalsciences,inparticular,independentverificationofdiagnosesanddrugdosagesshould bemade.Tothefullestextentofthelaw,noresponsibilityisassumedbyElsevier,authors,editorsor contributorsforanyinjuryand/ordamagetopersonsorpropertyasamatterofproductsliability, negligenceorotherwise,orfromanyuseoroperationofanymethods,products,instructions,orideas containedinthematerialherein.
Publisher: OliverWalter
AcquisitionEditor: SeanSimms
EditorialProjectManager: ThomasVanderPloeg
ProductionProjectManager: SreejithViswanathan
CoverDesigner: AlanStudholme
3251RiverportLane St.Louis,Missouri63043
ListofContributors TaruAggarwal AmityInstituteofBiotechnology AmityUniversityUttarPradesh Noida,UttarPradesh,India
HomicaArya BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
AdityaArya,PhD StaffScientist CentreforBioinformatics ComputationalandSystemsBiology PathfinderResearchandTrainingFoundation GreaterNoida,UttarPradesh,India
MalvikaBakshi BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
IvneetBanga AmityInstituteofBiotechnology AmityUniversity Noida,UttarPradesh,India DepartmentofBioengineering UniversityofTexas Dallas,TX,UnitedStates
SubhashiniBharathala CentreforBiomedicalTechnology AmityInstituteofBiotechnology AmityUniversity Noida,UttarPradesh,India
SagarikaBiswas,PhD SeniorPrincipalScientist DepartmentofGenomics & MolecularMedicine CSIR-InstituteofGenomics & IntegrativeBiology NewDelhi,India
PranjalChandra,MSc,MTech,PhD LaboratoryofBio-PhysioSensorsand Nanobioengineering DepartmentofBiosciencesandBioengineering IndianInstituteofTechnologyGuwahati Guwahati,Assam,India
DineshKumarChellappan DepartmentofLifeSciences SchoolofPharmacy InternationalMedicalUniversity BukitJalil,Malaysia
TrudiCollet,PhD IndigenousMedicinesGroup InstituteofHealth & BiomedicalInnovation QueenslandUniversityofTechnology Brisbane,QLD,Australia
VikramDalal DepartmentofBiotechnology IndianInstituteofTechnologyRoorkee Roorkee,Uttarakhand,India
ShrustiDave BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
KamalDua,PhD DisciplineofPharmacy GraduateSchoolofHealth UniversityofTechnologySydney Broadway,NSW,Australia
PriorityResearchCentreforHealthyLungs UniversityofNewcastle & HunterMedical ResearchInstitute Newcastle,NSW,Australia CentreforInflammation CentenaryInstitute Sydney,NSW,Australia
AkhilGajipara BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
SonuGandhi DBT-NationalInstituteofAnimalBiotechnology Hyderabad,Telangana,India
RishaGanguly DepartmentofBiochemistry UniversityofAllahabad Allahabad,UttarPradesh,India
AnamikaGangwar,MSc DefenceInstituteofPhysiologyandAlliedSciences Delhi,India
MonicaGulati,PhD SchoolofPharmaceuticalSciences FacultyofAppliedMedicalSciences LovelyProfessionalUniversity Phagwara,Punjab,India
AshutoshGupta DepartmentofBiochemistry UniversityofAllahabad Allahabad,UttarPradesh,India
GauravGupta SchoolofPharmaceuticalSciences JaipurNationalUniversity Jagatpura,Rajasthan,India
PhilipMichaelHansbro,PhD SchoolofLifeSciences FacultyofScience UniversityofTechnologySydney(UTS) Ultimo,NSW,Australia CentreforInflammation CentenaryInstitute Sydney,NSW,Australia PriorityResearchCentreforHealthyLungs UniversityofNewcastle & HunterMedicalResearch Institute
Newcastle,NSW,Australia
AshutoshKumar LaboratoryofBio-PhysioSensorsandNano bioengineering DepartmentofBiosciencesandBioengineering IndianInstituteofTechnologyGuwahati Guwahati,Assam,India
RameshKumar DepartmentofBiochemistry UniversityofAllahabad Allahabad,UttarPradesh,India
AmitKumar,PhD InternationalResearchCentre SathyabamaInstituteofScienceandTechnology Chennai,TamilNadu,India
KuldeepMahato LaboratoryofBio-PhysioSensorsandNano bioengineering DepartmentofBiosciencesandBioengineering IndianInstituteofTechnologyGuwahati Guwahati,Assam,India
PawanKumarMaurya,PhD AssociateProfessor DepartmentofBiochemistry CentralUniversityofHaryana Haryana,India
V.G.M.Naidu DepartmentofPharmacologyandToxicology NIPERGuwahati Guwahati,Assam,India
MastanMukramNaikwade DepartmentofPharmacologyandToxicology NIPERGuwahati Guwahati,Assam,India
RonyNunes,SPC LaboratoryofExtracellularMatrixandGeneExpression Regulation DepartmentofStructuralandFunctionalBiology InstituteofBiology UNICAMP,Brazil
BrianOliver,PhD SchoolofLifeSciences FacultyofScience UniversityofTechnologySydney(UTS) Ultimo,NSW,Australia
AbhayK.Pandey DepartmentofBiochemistry UniversityofAllahabad Allahabad,UttarPradesh,India
AkhileshKumarPandey DepartmentofSurgeryandNeurology TexasTechUniversityHealthSciencesCentre Lubbock,TX,UnitedStates
LilianCristinaPereira,PhD DepartmentofBioprocessesandBiotechnology CollegeofAgronomySciences(FCA)
SãoPauloStateUniversity(UNESP)-Centerfor EvaluationofEnvironmentalImpactonHuman Health(TOXICAM)
Botucatu,SãoPaulo,Brazil
BuddhadevPurohit LaboratoryofBio-PhysioSensorsandNano bioengineering DepartmentofBiosciencesandBioengineering IndianInstituteofTechnologyGuwahati Guwahati,Assam,India
ThaniaRiosRossiLima,MSc DepartmentofPathology BotucatuMedicalSchool SãoPauloStateUniversity(UNESP)-Centerfor EvaluationofEnvironmentalImpactonHuman Health(TOXICAM)
Botucatu,SãoPaulo,Brazil
SharmiliRoy LaboratoryofBio-PhysioSensorsand Nanobioengineering DepartmentofBiosciencesandBioengineering IndianInstituteofTechnologyGuwahati Guwahati,Assam,India
VijaylaxmiSaxena
BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
JuhiShah
BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
MaitriShah
BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
RutviShah
BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
DeepshikhaShahdeo DBT-NationalInstituteofAnimalBiotechnology (DBT-NIAB) Hyderabad,Telangana,India
AnmolShamal BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
PankajSharma,PhD Professor CentreforBiomedicalTechnology AmityInstituteofBiotechnology AmityUniversity Noida,UttarPradesh,India
AmitKumarSingh DepartmentofBiochemistry UniversityofAllahabad Allahabad,UttarPradesh,India
SanjaySingh,PhD AssociateProfessor DivisionofBiologicalandLifeSciences SchoolofArtsandSciences CentralCampus,AhmedabadUniversity Ahmedabad,Gujarat,India
AnanyaSrivastava DepartmentofPharmacologyandToxicology NIPERGuwahati Guwahati,Assam,India
PrachiThakore BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
NoopurThapliyal AmityInstituteofBiotechnology AmityUniversityUttarPradesh Noida,UttarPradesh,India
RoshikaTyagi AmityInstituteofBiotechnology AmityUniversity Noida,UttarPradesh,India
AkdasbanuVijapura BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
AashnaVyas BiologicalandLifeSciences SchoolofArtsandSciences AhmedabadUniversity CentralCampus Ahmedabad,Gujarat,India
RidhimaWadhwa FacultyofLifeSciencesandBiotechnology SouthAsianUniversity NewDelhi,India
KylieWilliams,PhD DisciplineofPharmacy GraduateSchoolofHealth UniversityofTechnologySydney Broadway,NSW,Australia
1 BiosensorsandTheirApplicationfor theDetectionofAvianInfluenzaVirus, 1 IvneetBanga,RoshikaTyagi, DeepshikhaShahdeoandSonuGandhi
2 Nanoparticle-MediatedOxidative StressMonitoring, 17 ThaniaRiosRossiLima,MSc RonyNunes,SPCand LilianCristinaPereira,PhD
3 NanoparticlesasModulators ofOxidativeStress, 29 RishaGanguly,AmitKumarSingh,Ramesh Kumar,AshutoshGupta,AkhileshKumar PandeyandAbhayK.Pandey
4 Nanomaterials-BasedNextGeneration SyntheticEnzymes:CurrentChallenges andFutureOpportunitiesinBiological Applications, 37 JuhiShah,ShrustiDave,AashnaVyas,Maitri Shah,HomicaArya,AkhilGajipara,Akdasbanu Vijapura,MalvikaBakshi,PrachiThakore,Rutvi Shah,VijaylaxmiSaxena,AnmolShamaland SanjaySingh,PhD
5 Nanoparticle-BasedDrugDeliveryfor ChronicObstructivePulmonary DisorderandAsthma:Progressand Challenges, 59
RidhimaWadhwa,TaruAggarwal, NoopurThapliyal,DineshKumarChellappan, GauravGupta,MonicaGulati,PhD TrudiCollet,PhD,BrianOliver,PhD KylieWilliams,PhD,PhilipMichaelHansbro, PhD,KamalDua,PhDand PawanKumarMaurya,PhD
6 BiosensorsinAnimalBiotechnology, 75 AdityaArya,PhD,AnamikaGangwar,MScand AmitKumar,PhD
7 Nanoparticle-MediatedOxidative StressMonitoringandRole ofNanoparticleforTreatment ofInflammatoryDiseases, 97 VikramDalalandSagarikaBiswas,PhD
8 BiomedicalApplicationsof Nanoparticles, 113 SubhashiniBharathalaand PankajSharma,PhD
9 CancerCytosensingApproachesin MiniaturizedSettingsBasedon AdvancedNanomaterialsand Biosensors, 133 BuddhadevPurohit,AshutoshKumar, KuldeepMahato,SharmiliRoyand PranjalChandra,MSc,MTech,PhD
10 Nanotherapeutics:ANoveland PowerfulApproachinModern HealthcareSystem, 149 AshutoshKumar,SharmiliRoy, AnanyaSrivastava,MastanMukramNaikwade, BuddhadevPurohit,KuldeepMahato,V.G.M. NaiduandPranjalChandra,MSc,MTech,PhD
INDEX, 163
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BiosensorsandTheirApplicationforthe DetectionofAvianIn fl uenzaVirus IVNEETBANGA • ROSHIKATYAGI • DEEPSHIKHASHAHDEO • SONUGANDHI
INTRODUCTION Avianinfluenzavirus(AIV),atypeAinfluenzavirus, belongstotheOrthomyxoviridaefamily.Itsgenetic makeupincludeseightnegative-sense,single-stranded RNAs.Itispleomorphicinnaturewithaverageparticle sizerangingbetween80and120nm.Theviralgenome isassociatedwithmanydifferentproteinssuchasnucleoprotein(NP)andtranscriptomecomplex(RNApolymeraseproteinssuchasPB1,PB2,andPA),which togetherformtheribonucleoproteins(RNPs).Thecell surfaceglycoproteinscomprisehemagglutinin(HA) proteinandneuraminidase(NA)proteinmajorly,and asmallnumberofM2proteinsarealsoexpressed, whichformtheionchannels.
AIVsinfectalargevolumeofthepoultryeveryyear andalsoposeaseverethreattohumanhealth.Between 1997and2008,theH5N1 AIVissaidtohaveledtoan economiclossof10billiondollarsinthepoultryindustry(Burnsetal.,2006).Accordingtoreports,AIVshave affectedapproximately62countriesworldwide,andthe numberisincreasingataveryfastpace,whereinnew casesarebeingreportedinbothanimalsandhumans.
Conventionaldiagnostictechniquesusedforthe detectionofAIVincludevirusisolationandscreening, polymerasechainreaction(PCR) basedassays,and enzyme-linkedimmunosorbentassays(ELISA).However,thesetechniquesarelabor-intensive,timeconsuming,andlesscost-effectiveandcannotbeused foron-sitemonitoring.ToreducetheyearlysocioeconomiclossduetoAIVs,thereisaneedfordevelopment ofadvancedtechniquesthatcanbeusedforearly diagnostics.Advancementsinthe fieldofbiosensors technologyhavepavedwayforthedevelopmentof diagnosticplatformsthathaveincreasedsensitivity andspecificity.Biosensorscanbeusedforon-sitemonitoringandasarapiddetectiontooltocontroldisease outbreaks.Inthischapter,wehavehighlightedthe molecularbiologyofAIVsandprincipleofdifferent
biosensorsdevelopedandappliedforeasyandquick detectionofAIVs.
AVIANINFLUENZAVIRUS:MOLECULAR BIOLOGY Influenzaisacontagiousdisease,whichiscausedby influenzaviruses.Influenzavirusesaremembersof theOrthomyxoviridaefamilyandcanbedividedinto threesubtypes,A,B,andCdependingonthecompositionofthenucleoproteinandmatrixprotein(Murphy andWebster,1996).AIVsbelongtotypeAinfluenzavirusandarecommonlyisolatedfromaswellasadapted toanavianhost.Thevirionsarequiteunstableinthe environmentandcaneasilybedegradedbyactionof heat,dryness,anddetergents(SwayneandHalvorson, 2003).
Thevirionsaregenerally80 120nmindiameter. TheAIVgenomecomprisesnegative-sense,singlestrandedRNAconsistingofeightfragmentsthatencode for10 11proteinswithintheviralenvelope.Thesegmentsandtheproteinsthattheyencodehavebeen describedin Table1.1.However,thearrangementof theseviralsegmentsisstillunderexaminationand notyetfullyunderstood.
TheoutermostlipidlayerofAIVarisesfromthe plasmamembraneofthehostinwhichthevirusreplicates(Nayaketal.,2009).Thousandsofprojectionsare presentonthesurfaceofthevirusparticlesintheform ofspikes.Around80%ofthesespikesareHAprotein, whereastherestaremadeupofNAproteins. Fig.1.1 illustratesthestructureoftheAIVparticle.Different strainsoftypeAvirusesarefounddependingonthe antigenicdifferencesofHA,cellsurfaceglycoproteins, andNAproteins(Burnsetal.,2006).CellsurfaceglycoproteinssuchasHAandNAarefoundinAIVinthe ratioof4:1.SomecopiesoftheM2proteinsarealso foundintheouterlipidmembraneofthevirusparticle,
TABLE1.1
Single-StrandedRNASegmentsPresentinAIV andtheProteinsTheyEncode.
Nameofthe
Segment Protein EncodedFunction
Segment1PB2 proteinFormspolymerase subunit
Segment2PB1 proteinFormspolymerase subunit
Segment3PAproteinFormspolymerase subunitand demonstrates proteaseactivity
Segment4HAproteinFormscellssurface glycoproteins
Segment5NPproteinFormsRNAbinding proteinand demonstratesnuclear importregulation
Segment6NAproteinHelpsinreleaseof virus,andforms surfaceglycoproteins
Segment7M1proteinFormsmatrixprotein
Segment8NS1andNS2/ NEPprotein Helpsinnuclear exportofRNAand regulateshostgene expression
whichplayasignificantroleinmaintainingtheion channelactivity(PielakandChou,2011).Ontheother hand,M1protein,oneofthemostabundantproteins foundinsidethevirus,aidsintheattachmentofthe RNP.RNPconsistsofapproximately50copiesof RNA-dependentRNApolymeraseandismadeupof threeproteins PB1,PB2,andPA(Boivinetal.,2010; Nodaetal.,2006).
Thereplicationprocessofthevirusparticlesmainly takesplaceinsidethenucleus.Thevariousstages involvedinthereplicationofAIV(Fig.1.2)aredivided into fivesteps:
1.Adsorptionofvirus,entryinsidethecelland uncoating
2.SynthesisofmessengerRNAandRNAreplication
3.Posttranscriptionalprocessing
4.Translationalandposttranslationalmodifications
5.Assemblyandreleasefromthecell
Replicationprocessbeginswiththebindingof AIVparticlestothesialicacidspresentonthecell surfaceasreceptors(SkehelandWiley,2000)andare internalizedbytheprocessofendocytosis,primarily clathrin-mediatedendocytosis.Insomecases,non clathrin-andnon caveolae-mediatedendocytosis pathwayshavealsobeenobservedduringvirusadsorption.Duringtheprocessofentryofvirioninsidethe cell,signalingprocessisactivated,whichfurtherfacilitatestheprocessofendocytosisandreleaseofviral RNPcontentintothecytoplasm(Elbaheshetal., 2014;Stegmann,2000).
FIG.1.1 Diagrammaticrepresentationoftheavianinfluenzavirusparticle.Theviralprojectionsarepresentin theformofspikesandarisefromthelipidenvelope.Mostoftheseprojectionsresemblerodsandaremadeof hemagglutininprotein,whereastheremainingmushroom-likeprojectionsaremadeofneuraminidaseprotein. SomecopiesofM2proteinarealsopresentonthemembrane.Presenceofmatrixprotein(M1)playsacrucial roleintheattachmentofRNPcomplex.
FIG.1.2 Replicationcycleoftheviralparticleinsidethehostbeginswiththeendocyticuptakeoftheviral particlebythehostfollowedbyendosomalreleaseoftheviralribonucleoproteininsidethecytoplasm.The RNPistransportedtothenucleuswhereitisusedasatemplateforthesynthesisofmRNAandRNA replication.Progenyvirionsaretransportedfromthenucleusontothecellsurfacewheretheyarereassembled, lysethecell,andreleased.
Insidethenucleus,thisviralRNPcontentisusedasa templateforthesynthesisofcDNA(complementary DNA)andviralmRNA(messengerRNA).ViralRNAdependentRNApolymerase,madeupofPA,PB1,and PB2,controlsthesynthesisofmRNA.Thenuclear exportofviralmRNAutilizesthe “machinery” ofthe hostcell,butisselective;exportiscontrolledbytheviral nonstructuralproteinNS1(Dengetal.,2005).
Viralproteins,mainlyNS2,NP,M1,andpolymerases,aretransportedtothenucleustocompletethe replicationprocessandaidinassemblyoftheviral particle.Progenyvirionsareassembledattheapical surfaceoftheplasmamembranefollowedbyexport ofnewlysynthesizedRNPsfromthenucleustothe plasmamembranetoallowtheirincorporationinto buddingvirions.
TalkingaboutthevirulencefactorsofAIV,thereislittleinformationknowninhostsotherthangallinaceous birds(suchaschickens,turkeys,andquail).Recently, evidencehasemergedabouttheimportanceof nonstructural(NS1)geneinthevirulenceofAIV (Basleretal.,2001;Lietal.,2006;Quinlivanetal., 2005).Moreover,ithasbeenobservedthatHA glycoproteinisanimportantmoleculardeterminant forpathogenicityofAIV.HA,whichissynthesizedas
aprecursormolecule,isactivatedbyposttranslational cleavagebyhostproteasestoobtainitsfullbiological properties.Whatisuniqueisthatthesequenceofthe proteolyticsiteisadeterminingfactorofthelevelof pathogenicity,thatis,willtheinfectionbesystemicof restrictedtosystemssuchasrespiratoryorenteric (TaubenbergerandMorens,2008).
Conventionaltechniquesusedforthedetectionof AIVareimmunohistochemicalassays,virusisolation, immunofluorescenceantibody(FA)test,ELISA,gene isolation,PCR-basedanalysis,sequencing,andmicroarray.However,thesemoleculardiagnostictechniques lacksensitivityandspecificity,requiretrainedpersonnel, cannotbeusedforon-sitemonitoring,andarenotcosteffective.Therefore,advancementsarerequiredinthe developmentofrapiddetectionmethodstoreducesocioeconomicburdenandprovidecost-effective,sensitive, specific,andquickdetectiontechnique.Advancements inthe fieldofnanotechnologyhaveledtothedevelopmentofbiosensorsthatcanbeusedfordiseasedetection ordetectthepresentoftargetanalyte/biomoleculepresentinbiologicalsamples.Itisimperativetoincorporate thefollowingcharacteristics(Fig.1.3)intobiosensorsso thattheycanbeusedasadiagnostictooltoincreaseits applicability.
FIG.1.3 Characteristicsofanidealbiosensor.Anidealbiosensorshouldbehighlyspecificindetectionofthe targetanalyte.Sensitivityofthebiosensordefinesitslimitofdetectionandhasagreateffectonitsusability. Developmentandmanufacturingofanidealbiosensorshouldbecost-effectiveinnaturetoincreaseitsonsite applicability.
BASICSOFBIOSENSORSTECHNOLOGY ThetermbiosensorwaspioneeredbyClarkandLyons withthedevelopmentoftheiroxygendetectingbiosensorsforblood.Itcanbedefinedasdiagnostictoolthat generatessignalbyinterpretingthebiophysicalor biochemicalinteractionswithbiologicalcomponents. Constructingabiosensorrequiressomebasicknowledgefromvarious fieldsofsciencesuchasphysics, chemistry,biology,microbiology,bioengineering,and nanoscienceforthekindofmaterials,devices,andtechniquesinvolved.Abiosensorisbasedontheprinciple ofsignaltransductionandprimarilycontainsabiosensinglayer,anorganicelementresponsiblefortheselectiveandspecificnatureofsensor,presenttodiscern anyparticularanalytefromtheinterestedmedium, andasensorelementthatrepresentsthesignaltransducingsegmentofthebiosensorsisresponsiblefor thegenerationofsignalandanelectronicsystemfor displaying,processingandamplification.Thesensing elementortransducercanmakeuseofmanytransducingmechanismssuchasoptical,magnetic,piezoelectric,andelectrochemical.Onthebasisoftheir transducer,therearedifferenttypesofbiosensorssuch aspiezoelectric,optical,electrochemical,andthermistorwithitsownsubtype.
Thebasicprinciplegoverningtheworkingof biosensor(Fig.1.4)istherecognitionofaspecificanalyte(biomolecule)bythereceptorandthenconverting thisbiorecognition(bioaffinityorbiometabolic)into quantifiablesignalbytransducer.Concentrationof theanalyteandintensityofgeneratedsignalsare directlyproportionaltoeachother.Thesesignalsare thenprocessedbyelectronicsystem.Forthecoupling ofbioelementandsensorelement,mainlyfourmechanismshavebeenused,i.e.,physicaladsorption,membraneimmobilization,covalentamalgamation,and matrixentrapment(Alietal.,2017).Aproductiveand efficientconstructionofahigh-performancebiosensors takeintoaccountverycrucialfactorssuchasimmobilizationofbioanalyteinitsnativeform,receptorsites availabilityforthespeciesofinterest,andaproductive adsorptionoftheanalyteonthesupportivemedium.
Biosensorscanbeclassifiedonthebasisofitstransducingelement(electrochemical,massdependent, optical,radiationsensitive,andsoon),bioanalyte (classesofDNA,glucose,toxins,mycotoxins,drugs,or enzymes),andsensingelement(enzyme,nucleicacid, proteins,saccharides,oligonucleotides,ligands,etc.) (Monosíketal.,2012;Turner,2000).Biosensorshave beenusedinvariousdisciplinessuchasmedicine,
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time of her admission to the Union in 1836 bitterly opposed having what is now the northern peninsula included within her territory in lieu of a ten mile wide strip of northern Indiana and Ohio, and it has been said that she nearly went to war to resist it. Even after the discovery of the iron ore deposits, no one realized the full importance of the minerals of this region.
S T M
O B W ,
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R , B
O P M
During the many years of campaigning for Federal help in the building of a canal at Sault Sainte Marie, the fisheries, valued at $1,000,000 a year, were given as the leading reason why a canal should be built, and it was no less a personage than Henry Clay, who, in opposing appropriation for this purpose, referred to the project and the district as “beyond the remotest settlement, if not in the moon.”
Now, within eighty years of that time, the annual tonnage of shipping passing through the Sault Sainte Marie canal is as great as the combined tonnage from the ports of New York, London, Liverpool, Antwerp, and Hamburg, and, as against the $1,000,000 value of the fisheries, the value at the mines of the ore alone shipped from this region amounts to about $100,000,000 yearly.
S O P M , C , M .
I H L O M
As the copper deposits are mostly along the shore of the lake and the great iron ore beds occur seven or more miles inland, the latter were not discovered until Sept. 19, 1844, when William A. Burt, a Deputy United States Surveyor, noticed that the needle of a solar compass of which he was the inventor became unreliable. In looking about to discover the magnetic source which must be the cause of the variation, members of his party discovered ore just beneath the sod near what is now Negaunee, Michigan. Inventor-like, Burt’s only concern was to devise some preventive for future interference by stray magnetic currents. He simply noted in his book that there was here a deposit of iron ore and neither he nor any of his party profited or apparently attempted to profit from the discovery.
S O B
S M M
The Indians seem to have had no previous knowledge of these ore deposits.
The first shipments of ore naturally were samples taken from what afterward came to be known as the Jackson mine and trials of them in blacksmiths’ forges were made at Jackson, Michigan (from which town went the first seriously-minded pioneer, Philo M. Everett), and at Cucush Prairie. They were soon afterward tried in a blast furnace at Sharon, Pa.
The first plan was to build forges and manufacture iron near the mines. So there was established on Carp River a forge to which the ore was hauled in winter when the ground was frozen. It turned out, however, that while very good bar iron was manufactured here, it could not be delivered in Pittsburg at a cost less than $200 a ton. As the market rate for iron then was but $80 a ton the plan was not financially successful.
Attention was turned to the shipping of ore to furnaces better located as regards coke supply and market. It was possible to make this a profitable undertaking only through cheap ore handling and transportation. So, to-day, the ore which is better adapted than the other raw materials for handling by labor-saving devices and
transporting without deterioration, is taken to the coke and limestone, and to the market for the product. While the weight of coke used is but half that of the ore smelted, its greater bulk, loss by breakage when handled in quantities, and deterioration upon exposure preclude its manipulation in the way which would be necessary to get it to the ore.
L F S M
The marvelous development of this territory into the greatest ore producer of the world, including the hauling of the first small shipment on mule back, the building of the plank and then the “strap” railroad with grades so steep that the small trucks often ran over and killed the mules, the building of the steam railroad, the successive building and enlarging of canal locks at Sault Sainte Marie connecting for use of ever larger and larger ore boats the waters of Lake Superior and Lake Michigan, and the growth of ore boat fleets to such size that during the shipping season scarcely ever is one boat out of sight of another over the entire 800 mile journey from Duluth to the furnaces along Lake Michigan and Lake Erie, is within the memory of men still living. Marquette was the shipping point during the earlier days and the history of this and adjacent regions during the latter half of last century vies in pioneering flavor with the tales
V H -R M , H , M .
of our early western frontiers, and with the more recent Yukon mining camps.
T R W
L S O G