Listofcontributors
AbdelwahebChatti LaboratoryofBiochemistryandMolecularBiology, FacultyofSciencesofBizerte,UniversityofCarthage,Jarzouna,Tunisia
AbdulShaban ResearchCentreforNaturalSciences,InstituteofMaterialsand EnvironmentalChemistry,Budapest,Hungary
AfefGamraoui LaboratoryofBiochemistryandMolecularBiology,Facultyof SciencesofBizerte,UniversityofCarthage,Jarzouna,Tunisia
AhmedBarhoum NanoStrucResearchGroup,ChemistryDepartment,Faculty ofScience,HelwanUniversity,Cairo,Egypt;NationalCentreforSensor Research,SchoolofChemicalSciences,DublinCityUniversity,Dublin, Ireland
AidaMousavi ResearchLaboratoryofSpectrometry&MicroandNano Extraction,DepartmentofChemistry,IranUniversityofScienceand Technology,Tehran,Iran
AminaOthmani FacultyofSciencesofMonastir,UniversityofMonastir, Monastir,Tunisia
AysuTolun InstituteofChemistry,FacultyofNaturalSciencesand Mathematics,TechnicalUniversityofBerlin,Berlin,Germany
AzamBagheriPebdeni DepartmentofLifeScienceEngineering,Facultyof NewSciences&Technologies,UniversityofTehran,Tehran,Iran
AzizAmine LaboratoryofProcessEngineeringandEnvironment,Facultyof SciencesandTechniques,HassanIIUniversityofCasablanca,Mohammedia, Morocco
BaharSaboorizadeh ResearchLaboratoryofSpectrometry&MicroandNano Extraction,DepartmentofChemistry,IranUniversityofScienceand Technology,Tehran,Iran
BoraGaripcan InstituteofBiomedicalEngineering,Bog ˘ azic¸iUniversity, Istanbul,Turkey
CansuIlkeKuru EgeUniversity,FacultyofScience,Departmentof Biochemistry,Izmir,Turkey
EcenazBilgen DepartmentofChemistry,MiddleEastTechnicalUniversity, C¸ankaya,Ankara,Turkey
EkinSehit InstituteofChemistry,FacultyofNaturalSciencesand Mathematics,TechnicalUniversityofBerlin,Berlin,Germany;Instituteof MaterialsScience,FacultyofEngineering,KielUniversity,Kiel,Germany
FahimehNojoki DepartmentofLifeScienceEngineering,FacultyofNew Sciences&Technologies,UniversityofTehran,Tehran,Iran
FereshtehAmourizi ResearchLaboratoryofSpectrometry&MicroandNano Extraction,DepartmentofChemistry,IranUniversityofScienceand Technology,Tehran,Iran
FranciscoJ.Barba NutritionandFoodScienceArea,PreventiveMedicineand PublicHealth,FoodSciences,ToxicologyandForensicMedicineDepartment, FacultyofPharmacy,UniversitatdeVale ` ncia,Vale ` ncia,Spain
FuldenUlucan-Karnak EgeUniversity,FacultyofScience,Departmentof Biochemistry,Izmir,Turkey
GilbertTang SchoolofAerospace,TransportandManufacturing,Cranfield University,Cranfield,UnitedKingdom
HayriyeO ¨ ztatlı InstituteofBiomedicalEngineering,Bog ˘ azic¸iUniversity, Istanbul,Turkey
IvanPetrunin SchoolofAerospace,TransportandManufacturing,Cranfield University,Cranfield,UnitedKingdom
JavadShabaniShayeh ProteinResearchCenter,ShahidBeheshtiUniversity, Tehran,Iran
JuditTelegdi ResearchCentreforNaturalSciences,InstituteofMaterialsand EnvironmentalChemistry,Budapest,Hungary;O ´ budaUniversity,Facultyof LightIndustryandEnvironmentalEngineering,Budapest,Hungary
KaiyuHe StateKeyLaboratoryforManagingBioticandChemicalThreatsto theQualityandSafetyofAgro-products;InstituteofAgro-productSafetyand Nutrition,ZhejiangAcademyofAgriculturalSciences,Hangzhou,P.R.China
KakaliGhoshal DepartmentofMedicine,DivisionofNephrologyand Hypertension,VanderbiltUniversitySchoolofMedicine,Nashville,TN, UnitedStates
KheibarDashtian ResearchLaboratoryofSpectrometry&MicroandNano Extraction,DepartmentofChemistry,IranUniversityofScienceand Technology,Tehran,Iran
LarbiEddaif O ´ budaUniversity,FacultyofLightIndustryandEnvironmental Engineering,Budapest,Hungary;ResearchCentreforNaturalSciences, InstituteofMaterialsandEnvironmentalChemistry,Budapest,Hungary
LiuWang StateKeyLaboratoryforManagingBioticandChemicalThreatsto theQualityandSafetyofAgro-products;InstituteofAgro-productSafetyand Nutrition,ZhejiangAcademyofAgriculturalSciences,Hangzhou,P.R.China
MariaHelenadeSa ´ CIQUP-ChemistryResearchCentreoftheUniversityof Porto,DepartmentofChemistryandBiochemistry,FacultyofSciences, UniversityofPorto,Porto,Portugal
MaryamAmoo NanotechnologyGroup,DepartmentofMaterialEngineering, IsfahanUniversityofTechnology,Isfahan,Iran
MehranHabibiRezaei DepartmentofCell&MolecularBiology,Schoolof Biology,CollegeofScience,UniversityofTehran,Tehran,Iran
MehrdadForough DepartmentofChemistry,MiddleEastTechnical University,C¸ankaya,Ankara,Turkey
MehrnoushDianatkhah DepartmentofClinicalPharmacy,Facultyof Pharmacy,IsfahanUniversityofMedicalScience,Isfahan,Iran
MuqsitPirzada InstituteofMaterialsScience,FacultyofEngineering,Kiel University,Kiel,Germany;InstituteofChemistry,FacultyofNaturalSciences andMathematics,TechnicalUniversityofBerlin,Berlin,Germany
NarjissSeddaoui LaboratoryofProcessEngineeringandEnvironment, FacultyofSciencesandTechniques,HassanIIUniversityofCasablanca, Mohammedia,Morocco
NavvabehSalarizadeh DepartmentofCell&MolecularBiology,Schoolof Biology,CollegeofScience,UniversityofTehran,Tehran,Iran;Departmentof Biochemistry,FacultyofMedicine,BaqiyatallahUniversityofMedical Sciences,Tehran,Iran
NedaShahbazi ResearchLaboratoryofSpectrometry&MicroandNano Extraction,DepartmentofChemistry,IranUniversityofScienceand Technology,Tehran,Iran
NissemAbdeljelil LaboratoryofBiochemistryandMolecularBiology,Faculty ofSciencesofBizerte,UniversityofCarthage,Jarzouna,Tunisia
OmerSadak DepartmentofElectricalandElectronicsEngineering,Ardahan University,Ardahan,Turkey
O ¨ zgu ¨ lPersilC¸etinkol DepartmentofChemistry,MiddleEastTechnical University,C¸ankaya,Ankara,Turkey
QingxinHui CranfieldWaterScienceInstitute,SchoolofWater,Energyand Environment,CranfieldUniversity,Bedford,UnitedKingdom
RichardLuxton InstituteofBio-SensingTechnology,UniversityoftheWestof England,Bristol,UnitedKingdom
RouholahZare-Dorabei ResearchLaboratoryofSpectrometry&Microand NanoExtraction,DepartmentofChemistry,IranUniversityofScienceand Technology,Tehran,Iran
SajjadShojai DepartmentofAnimalScience,SchoolofBiology,Collegeof Science,UniversityofTehran,Tehran,Iran
SanaSafariAstaraei ResearchLaboratoryofSpectrometry&MicroandNano Extraction,DepartmentofChemistry,IranUniversityofScienceand Technology,Tehran,Iran
SelmaHamimed LaboratoryofBiochemistryandMolecularBiology,Faculty ofSciencesofBizerte,UniversityofCarthage,Jarzouna,Tunisia
SeyedJalalZargar DepartmentofCell&MolecularBiology,Schoolof Biology,CollegeofScience,UniversityofTehran,Tehran,Iran
SeyedMohammadTaghiGharibzahedi IInstituteofChemistry,Facultyof NaturalSciencesandMathematics,TechnicalUniversityofBerlin,Berlin, Germany;InstituteofMaterialsScience,FacultyofEngineering,Kiel University,Kiel,Germany
SinanAkgo ¨ l EgeUniversity,FacultyofScience,DepartmentofBiochemistry, Izmir,Turkey
VahidMofid DepartmentofFoodSciences&Technology,NationalNutrition andFoodTechnologyResearchInstitute,FacultyofNutritionSciencesand FoodTechnology,ShahidBeheshtiUniversityofMedicalSciences,Tehran, Iran
WenliangLi CranfieldWaterScienceInstitute,SchoolofWater,Energyand Environment,CranfieldUniversity,Bedford,UnitedKingdom
XiahongXu StateKeyLaboratoryforManagingBioticandChemicalThreats totheQualityandSafetyofAgro-products;InstituteofAgro-productSafety andNutrition,ZhejiangAcademyofAgriculturalSciences,Hangzhou,P.R. China
YethrebMahjoubi LaboratoryofPlantToxicologyandEnvironmental Microbiology,FacultyofSciencesofBizerte,UniversityofCarthage, Zarzouna,Tunisia
YuweiPan CranfieldWaterScienceInstitute,SchoolofWater,Energyand Environment,CranfieldUniversity,Bedford,UnitedKingdom
ZahraGoli-Malekabadi BioengineeringCenterforCancer,Departmentof MechanicalEngineering,IsfahanUniversityofTechnology,Isfahan,Iran; DepartmentofBiomedicalEngineering,AmirkabirUniversityofTechnology, Tehran,Iran
ZeynepAltintas InstituteofMaterialsScience,FacultyofEngineering,Kiel University,Kiel,Germany;InstituteofChemistry,FacultyofNaturalSciences andMathematics,TechnicalUniversityofBerlin,Berlin,Germany
ZhugenYang CranfieldWaterScienceInstitute,SchoolofWater,Energyand Environment,CranfieldUniversity,Bedford,UnitedKingdom
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Listofcontributorsxiii
Abouttheeditorsxvii
Prefacexxi 1
Fundamentalaspects
1. Sensortechnology:past,present,andfuture3 MUQSITPIRZADAANDZEYNEPALTINTAS
1.1Introduction3
1.2Milestonesinsensordevelopment5
1.3State-of-the-artinsensortechnology7
1.4Thewayaheadinsensingopportunities9
1.5Conclusionsandremarks11 Acknowledgments12 References12
2. Fundamentalsofsensortechnology17 LARBIEDDAIFANDABDULSHABAN
2.1Sensor,actuator,andtransducerfundamentals17
2.2Sensors’classification23
2.3Sensorapplications31
2.4Innovativesensortechnologies39
2.5Conclusionandfutureaspects41 References42
2
Biomedicalapplications
3. Biosensorsforvirusdetection53 EKINSEHITANDZEYNEPALTINTAS
3.1Introduction53
3.2Antibody-basedbiosensorsforvirusdetection57
3.3Nucleicacid-basedbiosensorsforvirusdetection60
3.4Peptide-basedbiosensorsforvirusdetection65
3.5Molecularlyimprintedpolymer-basedbiosensorsforvirusdetection69
3.6Conclusionandremarks73 Acknowledgments74 References74
4. Biosensorsforbacteriadetection81
YUWEIPAN,WENLIANGLI,QINGXINHUIANDZHUGENYANG
4.1Introduction81
4.2Whole-cellbiosensorsforbacteriadetection82
4.3Nanomaterials-basedbiosensorsforbacteriadetection85
4.4Variousbiosensorsforbacteriadetection90
4.5Integratedbiosensingplatformsformultiplexedbacteriadetection112
4.6Conclusionandperspectives115 References116
5. Biosensorsfordrugofabusedetection125
KHEIBARDASHTIAN,FERESHTEHAMOURIZI,NEDASHAHBAZI,AIDAMOUSAVI, BAHARSABOORIZADEH,SANASAFARIASTARAEIANDROUHOLAHZARE-DORABEI
5.1Introduction125
5.2Drugbiosensing126
5.3Conclusionandremarks160 References161 Furtherreading172
6. Biosensorsfornucleicaciddetection173
MEHRDADFOROUGH,ECENAZBILGENANDOZGU ¨ LPERSILC¸ETINKOL
6.1Introduction173
6.2Opticalnucleicacidbiosensors:principlesandfeasibilities175
6.3Electrochemicalnucleicacidbiosensors188
6.4Strategiesforimprovingthesensitivityofnucleicacidbiosensors193
6.5CRISPR/Cas-assistedbiosensingplatformsfornucleicaciddetection202
6.6Biosensorapplicationsbasedonthenucleicacidstructure205
6.7Conclusionandoutlook212 References213
7. Biosensorsforglucosedetection235
EKINSEHITANDZEYNEPALTINTAS
7.1Introduction235
7.2Electrochemicalglucosebiosensors237
7.3Opticalglucosebiosensors244
7.4Otherglucosebiosensors251
7.5Conclusionandremarks254 Acknowledgments254 References254
8. Recentadvancesinbiosensingtechnologiesfordetecting hormones261 KAKALIGHOSHAL
8.1Introduction261
8.2Biosensortypesbasedonbiorecognitionelements263
8.3Biosensorsbasedontransducersinhormonedetection264
8.4Discussionandconclusion286 Acknowledgment290 Conflictsofinterest290 References290
9. Biosensorsforcancerbiomarkerdetection297 MUQSITPIRZADAANDZEYNEPALTINTAS
9.1Introduction297
9.2Cancerprogressandbiomarkers300
9.3Electrochemicalbiosensorsforcancerbiomarkerdetection306
9.4Opticalbiosensorsforcancerbiomarkerdetection311
9.5Piezoelectricbiosensorsforcancerbiomarkerdetection316
9.6Otherbiosensorsforcancerbiomarkerdetection319
9.7Conclusionandremarks320 Acknowledgments322 References322
10. Classicalandnewcandidatebiomarkersfordeveloping biosensorsindiagnosingdiabetesandprediabetes;past,present andfuture337
NAVVABEHSALARIZADEH,SAJJADSHOJAI,AZAMBAGHERIPEBDENI,FAHIMEHNOJOKI, SEYEDJALALZARGARANDMEHRANHABIBIREZAEI
10.1Introductiontodiabetesmellitus337
10.2Pathophysiologyofdiabetes339
10.3Glucoseasadiabetesbiomarker(history,accuracy,advantages,and disadvantages)345
10.4Glycatedhemoglobinandglycatedalbuminasdiabetesbiomarkers355
10.5Novelbiomarkers/metabolitesindiabetesandassociatedcomplications363 10.6Conclusion372 References373
11. Biosensorsfordrugdetection383 ZAHRAGOLI-MALEKABADI,NAVVABEHSALARIZADEH,MEHRNOUSHDIANATKHAH, MARYAMAMOOANDJAVADSHABANISHAYEH
11.1Introduction383
11.2Criteriaofanidealmethodfordruganalysis387
11.3Biosensordesign389
11.4Biosensorsfordrugdetection392
11.5Recenttrendsinbiosensorsfordrugdetection406 11.6Conclusion407 References408
12. Microalcoholfuelcellstowardsautonomouselectrochemical sensors413
MARIAHELENADESA ´
12.1Introduction413
12.2Fundamentals418
12.3Designandflowconsiderations423
12.4Fuelselectrooxidationandmicropowergeneration435
12.5Examplestowardsensingapplications452
12.6Conclusionandfutureoutlook458 References458
13. Biosensorsfororgans-on-a-chipandorganoids471 HAYRIYEOZTATLI,ZEYNEPALTINTASANDBORAGARIPCAN
13.1Introduction471
13.2Theuseofbiosensorsinorganotypicmodels473
13.3Biosensingtechnologiesformonitoringorganotypicmodels476
13.4Applicationsofbiosensorsininvitrocultureplatformsoforganotypic models488
13.5Conclusionandfutureperspectives500 Acknowledgments501 References501
3
Environmentalapplications
14. Sensorsforwaterandwastewatermonitoring517
ABDULSHABAN,LARBIEDDAIFANDJUDITTELEGDI
14.1Wastewaterpollutants517
14.2Sourcesofwaterpollutants517
14.3Typesofwaterpollutants518
14.4Indicatorsofwaterpollution522
14.5Analyticalmethodsforthedetectionofwastewaterpollutants528
14.6Chemicalsensorsinwaterpollutantdetection537
14.7Electrochemicalsensorsinwaterpollutantdetection541
14.8Opticalbiosensorsforwaterpollutiondetection546 14.9Conclusion555 References556
15. Chemicalsensingofheavymetalsinwater565 OMERSADAK
15.1Introduction565
15.2Heavymetaltoxicityrangesandmechanisminlivingcells567
15.3Heavymetalmeasurementmethodsinwaterandtheirperformance569
15.4Currenttrendsinheavymetalmonitoring582
15.5Currentlimitationsandfutureprospective584
15.6Conclusion585 References585
16. Chemicalsensingoffoodphenolicsandantioxidantcapacity593 AYSUTOLUNANDZEYNEPALTINTAS
16.1Introduction593
16.2Conventionalmethodsforthedeterminationoftotalphenolicsand antioxidantcapacity596
16.3Novelsensingmethodsoftotalphenolicsandantioxidantcapacity597
16.4Conclusion635 Acknowledgments636 References636
17. Chemicalsensingofpesticidesinwater647 KAIYUHE,LIUWANGANDXIAHONGXU
17.1Introduction647
17.2Colorimetricsensorsfordetectionofpesticides649
17.3Fluorescentsensorsfordetectionofpesticides652
17.4Ramansensorsfordetectionofpesticides654
17.5Electrochemicalsensorsfordetectionofpesticides657
17.6Chemiluminescentsensorsfordetectionofpesticides660
17.7Electrochemiluminescentsensorsfordetectionofpesticides662
17.8Piezoelectricsensorsfordetectionofpesticides663
17.9Conclusionandfutureperspectives665 References666
18. Chemicalsensorsandbiosensorsforsoilanalysis:principles, challenges,andemergingapplications669 SELMAHAMIMED,YETHREBMAHJOUBI,NISSEMABDELJELIL,AFEFGAMRAOUI, AMINAOTHMANI,AHMEDBARHOUMANDABDELWAHEBCHATTI
18.1Introduction669
18.2Detectionofsoilnutrients671
18.3DetectionofpH673
18.4Detectionofsoilmoisture675
18.5Detectionoforganicmatter676
18.6Detectionofinorganicpollutants680
18.7Soil-bornediseaseusingamicrobialbiosensor681
18.8Challengesandfutureperspectives692
18.9Conclusion693 References693
19. Recentadvancesinsensorandbiosensortechnologiesfor adulterationdetection699 NARJISSSEDDAOUIANDAZIZAMINE
19.1Introduction699
19.2Adulteration:aglobalscamandhealththreat700
19.3Conventionalanalyticaltechniquesforadulterantsdetection707
19.4Recenttrendsinadulterationdetection708
19.5Conclusionsandremarks725 References726
4
Constructionandotherapplications
20. Biosensingtechnologyinfoodproductionandprocessing743 SEYEDMOHAMMADTAGHIGHARIBZAHEDI,FRANCISCOJ.BARBA,VAHIDMOFIDAND ZEYNEPALTINTAS
20.1Introduction743
20.2Biosensorsandfoodquality758
20.3Biosensorsandfoodsafety786
20.4Futureprospectives798
20.5Conclusion799 Acknowledgments799 References800
21. Sensorsforaerial,automotive,androboticapplications825 IVANPETRUNINANDGILBERTTANG
21.1Introduction825
21.2Opticalsensors826
21.3Inertialsensors831
21.4Radiofrequencysensors833
21.5Magneticandacousticsensors839
21.6Timingsources842
21.7Finalremarks845 References846
22. Challengesandfutureaspectsofsensortechnology853 RICHARDLUXTON
22.1Introduction853
22.2Technologydrivers855
22.3Commercialization865
22.4Inconclusion869 References870 Furtherreading874
23. Sensorcommercializationandglobalmarket879 FULDENULUCAN-KARNAK,CANSU ILKEKURUANDSINANAKGOL
23.1Introduction879
23.2Trendsinsensingtechnologies881
23.3Sensingresearchanddevelopment889
23.4Commercializationpathway890
23.5Sensorsinvariousindustrialareasandglobalmarketshares899
23.6Conclusion906 References907 Index917
Sensortechnology:past,present, andfuture
MuqsitPirzada1,2 andZeynepAltintas1,2
1InstituteofChemistry,FacultyofNaturalSciencesandMathematics, TechnicalUniversityofBerlin,Berlin,Germany, 2InstituteofMaterials Science,FacultyofEngineering,KielUniversity,Kiel,Germany
1.1Introduction
ModernsensorsarevastlydifferentfromtheprimitiveoxygenelectrodedevelopedbyClarknearlysevendecadesago [1].Asurveyofall databasesfromWebofScience(keywords:sensor/sORbiosensor/s) revealsthatinterestinsensortechnologyhasexplodedinrecenttimes withnearly1.5millionpaperspublishedwithinthelast40years.Ofthese, morethanamillionhavejustbeenpublishedsince2009.Thisexponential progress(Fig.1.1)canbeattributedtothemultifoldimprovementinseveralscientificdisciplinessuchaselectrochemistry,optics,nanotechnology, moleculardynamics,andproteomics.Anothertriggerforthissuccessis therisingdemandforanalyterecognitionacrossvariousfieldsofapplication.Forexample,identifyingandanalyzingcontaminantsinfoodproductionisaprerequisitetoensuringalongshelf-lifeaswellasconsumer safety.Accumulationofmicrobialmetabolicbyproductshelpsidentifythe freshnessofmeatandfish [2].Thelevelsofsuchmetabolitesandproteins inlivingbeingsmayalsoactasearlyindicatorsofdifferenthealthconditions [3].Quantifyingthesemarkershelpsidentifydiseases,riskfactors, pregnancyaswellasdrugefficacy.Biosensorsalsohelpmonitortheeffectivenessofclinicaltherapiestherebyenablinghealthcareprofessionalsto customizepatient-specifictreatments.Thetrendisalsoreflectedinthe commercialprogressofsensinginstrumentswherethecontributionofbiosensorshasswelledfromUS$5milliontoUS$13billionwithinthree
FIGURE1.1 Researchworksonsensorspublishedbetween1975and2020.Inset: Researchworksonsensorsforpoint-of-caretestingpurposesfrom1990to2020. Source: DatafromWebofScience.
decades [4].Sincethedevelopmentofthefirstcommercialbiosensorin 1975,thenumberandvarietyofsensorshaveconsistentlyincreasedto morethan40,000productsforinvitrodiagnosticsalone [5].
Althoughconventionaldiagnosticsarestillperformedatcentralized facilitiesbyexperiencedprofessionals,thecripplingdeficiencyofmaterial andfinancialresourcesinunderdevelopedanddevelopingnationsmakes timelydiseaserecognitionnotonlytime-consumingbutalsoexpensiveand inaccessibletothegeneralpublic.ThereforetheWorldHealthOrganization hasencouragedthedevelopmentofpoint-of-care-tests(POCT)thatmeet theASSURED(Affordable,Sensitive,Specific,User-friendly,Rapidand robust,Equipment-freeandDeliverabletoend-users)criteriaandcanbe performedbytheconsumerinanonclinicalsetting.Asaresult,the researchanddevelopmentofPOCTdeviceshavemultiplied130-foldfrom 1990to2020(Fig.1.1,inset).Sensortechnologyisthereforegravitating towardpaper-basedassays,lateralflow-tests,smartphone-baseddetection, andmanysimilarapproachesthatrely onubiquitousrawmaterialsand instruments.Today,arduousexperimentaloptimizationsarebeingreplaced withcomputationalsimulations.Severaldifferenttypesofnanomaterials arebeingincorporatedinbiosensors toamplifytheirsignal,reducethe responsetimeandimprovethebindingaffinity [6].Miniaturizationofbiosensorsusingmicrofluidictechnologyhelpsinreducingthesamplevolume requiredforanalysis.Microfluidictechnologyisanintegralpartoflab-ona-chipandorgan-on-a-chipsystems.
Thespecificityofsensingsystemstorecognizeatypicalanalytecan beexploitedfortargeteddrugdeliveryandtherapy.Suchapproaches reducetheadverseside-effectsthatarequotidianinthetreatmentof
cancerpatients.Invivosensingisalsousefulinthedevelopmentofartificialorganstoregulateorganbehaviorinresponsetovariousintracellularsignalingevents [7].Theongoingglobalcoronaviruspandemichas alsodirectedrenewedinteresttowardbiosensorsaspotentialtoolsfor identifyingandcurbingwateraswellasairpollution [8,9].
1.2Milestonesinsensordevelopment
ThecurrentubiquityofsensorsshouldnotbeconsideredasastandalonesuccessresultingsolelyfromCramer’sworkontheglasselectrode [10] orevenClark’sseminalresearchonbiosensors [1,11].Whilethese workslaidthegroundworkonwhichsensortechnologyisbuilt,thelatestdevelopmentsinbiosensorsaretheproductsofadvancements,discoveries,andinventionsacrossagamutofscientificareas.Afewof theseconceptsevenpredateClark’sworkbuthavestillemergeduseful insensordevelopment.Forexample,whilePolyakov’sgroupwasworkingwithsilicaparticlesin1931,theyobservedthatparticlesfromwhich theadditiveswereremovedshowedenhancedadsorptionfortheadditivesincomparisontostructurallyanalogousligands [12].Dickey substitutedtheseadditiveswithdyesastemplates [13].Thisconceptof additivememoryevolvedintomolecularimprintingtechnology,apopulartechniqueforcost-effectivemolecularrecognition.Molecular imprintinghasitselfundergoneseveralimprovementsintheninedecadessinceitsinception.Thesilicaparticleshavelargelybeenreplaced withorganicpolymerssince1972 [14].ThereforeMosbach’sgroupproposedusingsuchmolecularlyimprintedpolymers(MIPs)tomimicantibodies [15].
Molecularimprintingisnotasingularfield.Theimpetustomake sensors“moreintelligent”wasthedrivingforcebehindthediversificationofsensortechnology.Initsearlyphase,sensordevelopmentwas aneccentricnotioninvolvingtheintegrationofbiomoleculessuchas enzymestoelectrochemicalsensingelementssuchaselectrodes. Althoughthefirstbatchofsensorsreliedoneithervoltammetryor amperometry,otherelectrochemicalmethodssuchaspotentiometry weresoonexplored.Theprimitiveenzymeelectrodesofthe1960swere improvisedbyProfessorRechnitzin1971byplacingtheminan invertedconfigurationforbetaglucosidase-mediatedamygdalinesensing [16].Thision-selectiveelectrodesparkedarenaissanceageinsensor developmentwheremultiplecombinationsofthetransducerandthe biologicalelementwereprobed.
Thevariationsintheseelementsandtheircombinationsarestill ongoing.Sensorshavebeendevelopedwithpiezoelectric,thermal,and thenopticaltransducers.Thiscontinuousevolutionfacilitatedthe
developmentofthefirstinvivoultrasoundbiosensorin2020 [17].The selectionofreceptorshasalsoevolvedfromenzymestoantibodies, nucleicacids,wholecells,aptamers,affibodies,phages,andsynthetic ligands.Althoughtheenzymeswerethereceptorofchoiceinthefirst fewyearsofsensordevelopmentandwereusedbyseveraleminent researcherslikeClark [11],UpdikeandHicks [18],Guilbaultand Montalvo [19],antibody-assistedbiomoleculerecognitionwasalsobeing investigatedinparallel.Theantibody-antigeninteractionhadremained anenigmasincethediscoveryofantibodiesin1890 [20].Oncethese interactionsweretheorizedbyGoldbergin1952 [21],theirsuitabilityfor diseaserecognitionwassooninvestigated.Withinfouryears,thelatex agglutinationassaywasdevelopedthatreliedontheseinteractionsto diagnoserheumatoidarthritis.YalowandBersonsubsequentlydevelopedthefirstimmunoassay,aradioimmunoassay,in1959forwhich YalowwasawardedtheNobelPrizein1977 [22].Sincetheradioimmunoassaywasnotpatented,assaysforseveraldifferentanalyteswere soondeveloped.Asthistechniqueinvolvedantibodylabelingwith radioactiveisotopes,alternativelabelswerestudiedinthe1960sand antibody-enzymelinkswerereportedin1966 [23,24],whichlaidthe groundworkforthefirstenzyme-linkedimmunosorbentassaywithin thenext5years [25].Anotherpivotalmilestoneinimmunosensingwas thedevelopmentofmonoclonalantibodiesbyKohlerandMilsteinin 1975 [26].Theprocesswasrevolutionaryandmitigatedthepertinent issuesoflimitedantibodysupplyandunavailabilityculminatingina NobelPrizeinmedicineforboththeresearchersin1984.Someofthe popularassaysdevelopedduringthistimeareillustratedin Fig.1.2 Similarmilestoneswerealsoachievedinthefieldofdetectionusing nucleicacidsaswellaswholecellsormicrobes.Enzymes,antibodies, nucleicacids,andwholecellsaregenerallyconsideredconventional
FIGURE1.2 (A)Differenttypesofenzyme-linkedimmunosorbentassays(ELISA);(B) Gelelectrophoresis,whichisthebasisofSouthern,Western,Northern,andEasternblot tests;(C)Antigenrecognitionbyradioimmunoassay.
receptors.Whileenzymaticreceptorsfunctionduetocatalysis,allother elementsperformaffinity-basedrecognition.Recentreceptorssuchas syntheticantibodies,phages,affibodies,andaptamersareemergingas promisingsubstitutestotheconventionalreceptorsandmayentirely replacetheminthefuture.
1.3State-of-the-artinsensortechnology
Theprevalenceandsuccessfulapplicationofsensorsareincumbent onseveralfactorssuchastheircost,responsetime,sensitivity,specificityinthesensingmedium,andtheirabilitytodetectmultipleanalytes. Thedrivetoattainultrasensitivityhasresultedintheintegrationof severalunconventionaltechnologiesintosensordevelopment.For example,theincorporationofnanomaterialstosensingplatformshas enabledthefabricationofsensorswithhighsensitivityandspecificity. Nanomaterialsarematerialswithatleastoneoftheirdimensions between1and100nm [6].Owingtotheirsmallsize,nanomaterials exhibitanexceptionallyhighsurfacearea-to-volumeratio.Smaller nanomaterialssuchasnanoclustersandquantumdotshavemoreatoms ontheirsurfaceincomparisontothebulk.Thehigh-energyelectrons fromthesesurfacesgiverisetointerestingplasmonicandelectronic properties.Nanomaterialscanactassyntheticatomsandtheirpropertiescanbetunedbycontrollingtheirsize,shape,orinterparticledistance.Forexample,thedistancebetweenaquantumdotandagold nanoparticlecanbemodulatedwithlinkerstodeterminetheoptimal distanceformaximumlocalizedsurfaceplasmonresonance [27].The incorporationofnanoparticlesintothesensingplatformalsohelps amplifythesignalresponsesignificantly [3].Nanomaterialsholdthe keytosensorminiaturizationsincetheycanbeexploitedasreceptors, transducers,labels,fluorophores,andsignalamplificationtags [28–31]. Nanotechnologyhasthereforeachievedpopularitynotonlyamongsensordevelopersbutalsoamongthescientificcommunityasawhole. ThisrecognitionisevidentwiththemultitudeofNobelPrizesawarded forresearchinthisareasuchasKroto,Curl,andSmalley’sdiscoveryof buckminsterfullerene(Chemistry,1996),FertandGruenberg’sdiscovery ofgiantmagnetoresistance(Physics,2007),GeimandNoselov’sexperimentsongraphene(Physics,2010),andSauvage,Stoddart,and Feringa’ssynthesisandresearchonmolecularmachines(Chemistry, 2016).AbriefsurveyoftheScopusdatabase(keywords:sensor/sOR biosensor/sANDnanomaterial/s)acrossallfieldsrevealsthatjust withinthetwodecadessince2001,167,774documentswerepublished onnanomaterial-mediatedsensorsand129,300areresearcharticles. Whileonly85ofthesedocumentsbelongto2001,thenumberrose
FIGURE1.3 Researchworksusingnanomaterialsinsensortechnologyfrom2000to 2020. Source:DatafromScopus.
rapidlywith4183and31,174documentsreportedannuallyin2010and 2020,respectively(Fig.1.3).
Mathematicalmodelingisanotheremergingtoolthatisusefulfor fabricatingbiosensingplatformswithdesiredfeatures.Itallowsthe optimizationofmultiplecriteriawithinthebiochemicalsystemsuchas enhancingtheproductivityofenzymesbydeterminingtheaccurate temperatureandpHrequiredforcatalyticrecognition.Computational selectionofnucleicacidprobesbyquantifyingtheinteractionsbetween Watson-Crickbasepairsfacilitatesthegenerationoftarget-specificand ultrasensitivegenosensors [32].Cascadenetworkscanthusbegenerated toperformdivergentreactionsbyexploitingthecompatibilitybetween variousbiomolecules.Insilicobiocomputationhasalsobeenadopted forsystemsthatinvolveproteins [33],aptamers [34],wholecells [35] as wellasMIPs [36].Molecularsimulationsoftencomputetheattractive andrepulsiveforcesofbiomolecularelectroncloudstopredictthestate ofmaterialduringthesensingevent.Forexample,thegroupofAltintas simulateddifferentsurfaceepitopesofaproteintoselectthemoststabilepeptidesequenceastemplatesformolecularimprints [36].Such simulationsaidinelucidatingsolventeffects [37] aswellasthenature ofreceptor-ligandinteractions [38].Biocomputationinassociationwith logic-mediatedoperationsencouragesthedevelopmentofartificialneuralnetworks.Theseintelligentsystems,whenintegratedintosmart stimuli-responsivematerials,arecapableofsensingandsubsequently actuating [32].Insilicodesigningofbiosensorsconsiderablyreducesthe experimentalload,materialconsumptionaswellasoptimizationand developmenttime.
Thebindingaffinityandspecificityaretwoessentialfeaturesofthe receptorthatenablemoleculerecognitionatlowconcentrationsinthe presenceofcompetentinterferingmolecules.Aptamersareoligonucleotidesorpeptidesthatspecificallybindtoatargetnucleotide,protein,or cell.Theybelongtotheclassofnovelreceptorsalongwithphages, MIPs,andaffibodies.Althoughthetechnologyforaptamersynthesis andenrichment(systematicevolutionofligandsbyexponentialenrichmentor“SELEX”)wasalreadydevelopedin1990,theywerefirst employedforbiosensingonlyin1998 [39,40].However,aptamershave becomecommonplaceasreceptorssincethenandhavealreadysurpassednucleotidessuchasdeoxyribonucleicacid(DNA)andribonucleicacid(RNA).TheongoingtrendonScopus(keywords:biosensor “AND” , receptortype . )reflectsthepotentialforaptamerstosurpass antibodiesasthereceptorofchoicewithinthenextfewdecades. Similarly,bacteriophagesarealsosuitablecandidatesduetotheirhigh affinityforbacterialproteins.Thephagedisplaytechniquewasfirst reportedbyGregorySmithin1985 [41] andfurtherdevelopedby GregoryWinterforwhichbothofthemsharedtheNobelPrizeinchemistryin2018.Thephagedisplaytechniqueinvolvestheinsertionofa gene,whichencodesaproteinorantibodyofinterest,inbacteriophage capsidprotein.AnalogoustoSELEX,phagedisplayisapromising invitrotechniqueforproteinselection.
1.4Thewayaheadinsensingopportunities
Theongoingpandemicandthepressureonthehealthcaresystem resultingfromithaveacceleratedtheresearchonPOCT.Microfluidic systemscanbeeasilypatternedoninexpensivesubstratessuchas papersormembranestogeneratelateralflowassays.Thesimplicity, mobility,andaffordabilityoflateralflowassaysmakethemidealfor diseasedetectioninresource-limitedsettings.Forexample,thenecessity ofacoronavirusdisease(COVID-19)testreporthasbecomeaprerequisitefortravel,workaswellasschoolsandtheusualpolymerasechain reactionassayisexpensive,time-consuming,andcomplicated.Rapid lateralflowimmunoassaysfordetectingthecoronavirusantigencanbe mass-producedandareverysimpletooperatebytheend-consumer [42].TheyarethereforetransformingintoexcellentCOVID-19screening tests.Itisexpectedthatjustlikethecaseofhomepregnancykits,diseasetestingonlateralflowstripsmayalsobecomequotidianespecially indevelopingnations(Fig.1.4).
AnotherpromisingstrategyistheuseofMIPsassynthetic antibodiesforproteinrecognition.ThoughMosbachproposedtheidea fordrugrecognitionbackinthe1990s,proteinrecognitionusingtheir
