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Electrochemical affinity sensors for biomedical, food and environmental applications

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(1)Electrochemical affinity sensors for biomedical, food and environmental applications Anca Stefana Florea. To cite this version: Anca Stefana Florea. Electrochemical affinity sensors for biomedical, food and environmental applications. Analytical chemistry. Université Claude Bernard - Lyon I, 2015. English. �NNT : 2015LYO10126�. �tel-01233083�. HAL Id: tel-01233083 https://tel.archives-ouvertes.fr/tel-01233083 Submitted on 24 Nov 2015. HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés..

(2) N° d’ordre: 126-2015. Année 2015. THESE DE L’UNIVERSITE DE LYON Délivrée par L’UNIVERSITE CLAUDE BERNARD LYON 1 ECOLE DOCTORALE: Chimie Spécialité: Chimie DIPLOME DE DOCTORANT (Arrêté du 7 août 2006) Soutenue publiquement le 14 Septembre 2015 Par Mlle FLOREA Anca Stefana TITRE:. Electrochemical affinity sensors for biomedical, food and environmental applications JURY: Rapporteurs: Prof. Dr. Camelia Bala Dr. Serge Cosnier Examinateurs: Dr. Cecilia Cristea Dr. Joelle Saulnier Directeurs de these: Dr. Nicole Jaffrezic-Renault Prof. Dr. Robert Săndulescu.

(3) . .  ʹ. AncaftefanaFlorea. . . .

(4) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. . ͵ . Dr. Christopher A. Mills Directeurs de these: Prof. Abdelhamid Errachid-El-Salhi Dr. Nadia Zine      “Iamnotyoungenoughtoknoweverything” OscarWilde   .  Dedicatedtomyfamily  . .

(5)  Ͷ . AncaftefanaFlorea. Acknowledgements There are more people that I can countwhohelped making this work possible. I oweahugedebtofgratitudetomysupervisors,mycoworkers,myfamilyandmyfriends. I would like to express my deepest gratitude to my supervisors Prof. Dr. Robert SãndulescuandDr.NicoleJaffrezicǦRenaultfortheopportunitytoworkintheirexcellent researchgroups.Theirconstantsupport,valuabletime,constructiveadvicesandpositive attitude and confidence towards me have been wholehearted and made me believe in myselfasaresearcher. I owe a big debt of gratitude to Dr. Cecilia Cristea forher friendship, continuous support,confidenceinmeandpreciousadvicesinbothmyworkandlife. I am greatly appreciative to prof. Dr. Giovanna Marrazza from Univeristy of Florenceforherguidanceandsupportandtodr.AndreaRavalliforhisvaluableadvices andhelp. Ialsothankthecomiteefortheadvicesandhelpinimprovingmythesis. I owe special thanks to all my collegues and friends from the Department of Analytical Chemistry Cluj, from ISA Lyon and “Ugo Shiff” Department Florence, who contributednotonlytoworkbutalsotomakingitfun.Therearecountlesspeoplethat have been helpful throughout time and with whom I shared great experiences, so I apologize in advance for forgetting naming some of them. Thanks to Bogdan, Andreea, Mihaela, Lumi, Bibi, Oana, whose advices, friendship and support was essential to my progress.IthankCoco,RebeccaandDiegofortheirfriendshipandcheerfulnessandfor makingFlorencehomeforme.IamgreatlythankfultoMamisforthesupport,friendship and good spirit all along the way. I am grateful to fam. Lacroix for their hospitality during my staying in Lyon. I would like to thank to all doctorants in ISA Lyon, Elena, Sylvia,Nedjla,Mohamed,Vika,Katyaetc,forthememorableexperiencesinandoutside workinLyon.ToZhenZhong,HuyandMadihafortheircollaborationandhelpregarding MIPsensors.SpecialthankstoAlvaroforhisfriendshipandencouragement.Ialsothank Eliforherfriendship,cheerfulnessandinspiration. Iwouldliketothankallmyfriendsfortheirsupportandunderstanding. Finnaly,Iamdeeplythankfultomyparents,mybrother,mysisterǦinǦlawandto mywholefamilyfortheirendlesslove,encouragementandsupport.Wordstrulycannot expresshowluckyIfeeltohavehadthemeverystepalongtheway.   .

(6) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ͷ . 

(7)  ‡ ˆ”ƒ­ƒ‹•ǣ Capteurs électrochimiques d’affinité applique dans l’analysebiomédicale,sécuritéalimentaireetenvironnementale  ‡ˆ”ƒ­ƒ‹•ǣ ‡• ƒ’–‡—”• ±Ž‡ –”‘ Š‹‹“—‡• •‘– †‡• ‘—–‹Ž• ’‘—” Žƒ †±–‡ –‹‘ ˆ‹ƒ„Ž‡ǡ ’‡— ‘ð–‡—šǡƒ˜‡ —‡Šƒ—–‡•‡•‹„‹Ž‹–±‡–•±Ž‡ –‹˜‹–±ǡ’‘—”Žƒ†±–‡”‹ƒ–‹‘†‡• ‘’‘•±• „‹‘Ž‘‰‹“—‡•‡– Š‹‹“—‡•†ƒ•Ž‡•†‘ƒ‹‡•†—†‹ƒ‰‘•–‹  Ž‹‹“—‡ǡŽ̵‡˜‹”‘‡‡–‡– Ž̵‹†—•–”‹‡ƒŽ‹‡–ƒ‹”‡Ǥƒ”–‹ —Ž‹°”‡‡–ǡŽ‡•

(8) —‘ ƒ’–‡—”•ǡƒŽŽ‹ƒ–—‡–”°•‰”ƒ†‡ •’± ‹ˆ‹ ‹–±Ǥ2‰ƒŽ‡‡–†‡•‘—˜‡ƒ—š–‡ Š‹“—‡•’”‘†—‹•‡–†‡•”±•—Ž–ƒ–••‹‹Žƒ‹”‡•ǡ’ƒ” ‡š‡’Ž‡ǡŽ‡• ƒ’–‡—”•„ƒ•±••—”Žƒ–‡ Š‹“—‡†‡•‘Ž›°”‡•‡’”‡‹–‡‘Ž± —Žƒ‹”‡ǡŽƒ “—‡ŽŽ‡’”‘†—‹•‡†‡•”± ‡’–‡—”•ƒ”–‹ˆ‹ ‹‡Ž•Ǥƒ–‡ Š‹“—‡†‡˜‹‡––”°•‹’‘”–ƒ–†ƒ•Ž‡• • ‹‡ ‡• „‹‘ƒƒŽ›–‹“—‡• ’ƒ” ‡ “—ǯ‹Ž ’‘”–‡ †‡• ƒ˜ƒ–ƒ‰‡• ‹Š±”‡–• •—” Ž‡• ”± ‡’–‡—”• ƒ–—”‡Ž•ǣ —‡ ‰”ƒ†‡ •–ƒ„‹Ž‹–± †ƒ• †‡• †‹ˆˆ°”‡– ‡˜‹”‘‡‡– ‡– ‘†‹–‹‘•ǡ ±‰ƒŽ‡‡– ‘’–‡–ƒ˜‡ —‡‰”ƒ†‡ˆŽ‡š‹„‹Ž‹–±†ƒ•Žƒ ‘ ‡’–‹‘ǡ—‡Žƒ”‰‡‰ƒ‡ †‡‘Ž± —Ž‡•’‡—˜‡–²–”‡—–‹Ž‹•±‡•Ǥ ̵‘„Œ‡ –‹ˆ †— –”ƒ˜ƒ‹Ž ’”±•‡–± ‹ ‹ ‡•– †‡ †±˜‡Ž‘’’‡” †‡• ƒ’–‡—”• ±Ž‡ –”‘ Š‹‹“—‡• ƒ˜‡  —‡ –”°• ‰”ƒ†‡ ƒˆˆ‹‹–± ‡– •’± ‹ˆ‹ ‹–± ’‘—” —‡ ƒƒŽ›–‡Ǥ ‡• “—‡ŽŽ‡• ‘’”‡‡– †‡• ƒ’’Ž‹ ƒ–‹‘• –”°• †‹˜‡”• ‘‡ †ƒ• Žƒ ’”‘–‡ –‹‘ †‡ Ž̵‡˜‹”‘‡‡–ǡŽƒ•± —”‹–±ƒŽ‹‡–ƒ‹”‡‡–Ž‡†‘ƒ‹‡„‹‘±†‹ ƒŽǤƒ’”‡‹°”‡’ƒ”–‹‡ †‡ Žƒ –Š°•‡ ’”±•‡– Ž̵±–ƒ– ƒ –—‡Ž †‡ Žƒ ‘ ‡’–‹‘ ‡– –‡ Š‹“—‡• †‡ ˆƒ„”‹ ƒ–‹‘ †‡• „‹‘ ƒ’–‡—”•Ǥ •—‹–‡ǡ Ž‡• ƒ•’‡ –• ‰±±”ƒ—š †‡• ‹—‘ ƒ’–‡—”• ±Ž‡ –”‘ Š‹‹“—‡• ‡– ƒ’–‡—”• „ƒ•‡ •—” †‡• ƒ’–ƒ°”‡• •‘– ’”±•‡–±• ‹ ‹ǡ ƒ‹•‹ “—‡ ’Ž—•‹‡—”• ‡š‡’Ž‡• ”ƒ’’‘”–±• †ƒ• Žƒ Ž‹––±”ƒ–—”‡ ’‘—” Žƒ †±–‡ –‹‘ †‡ ƒ”“—‡—”• „‹‘Ž‘‰‹“—‡• †— ƒ ‡”Ǥ ‡• ƒ˜ƒ–ƒ‰‡• †‡ Ž̵‹–±‰”ƒ–‹‘ ƒ‘ƒ–±”‹ƒ—š †ƒ• Ž‡• †‹•’‘•‹–‹ˆ• †‡ †±–‡ –‹‘ •‘– ’”±•‡–±•Ǥ •—‹–‡ǡ ’Ž—•‹‡—”• ƒ•’‡ –• •—” Žƒ –‡ Š‹“—‡ †‡• ‘Ž›°”‡•  ‡’”‡‹–‡ ‘Ž± —Žƒ‹”‡•‘–‹–”‘†—‹–•Ǥ ƒ ’ƒ”–‹‡ ’‡”•‘‡ŽŽ‡ †‡ ‘–”‹„—–‹‘ ‡•– •–”— –—”± ‡ –”‘‹• Šƒ’‹–”‡•ǣ ‡ ’”‡‹‡” –‡’• Žƒ ±–Š‘†‘Ž‘‰‹‡ ‡– Ž‡• ”±•—Ž–ƒ–• ‘„–‡—• ’‘—” Ž‡ †±˜‡Ž‘’’‡‡– †‡ †‡—š ‡••ƒ‹• „‹‘Ž‘‰‹“—‡• ’‘—” Žƒ †±–‡ –‹‘ †— ƒ”“—‡—” –—‘”ƒŽ — ‹ͳǤ ‡ ’”‡‹‡” Šƒ’‹–”‡ ‡•– †±†‹± •—” — ƒ’–‡—”  „ƒ•‡ †‡ „‹ŽŽ‡• ƒ‰±–‹“—‡•ǡ †ƒ• Ž‡ †‡—š‹°‡ Šƒ’‹–”‡—‡ ƒ’–‡—”ƒ’–ƒ°”‡„ƒ•‡•—”†‡•ƒ‘’ƒ”–‹ —Ž‡•†̵‘”•ƒ•ƒ— —ƒ”“—ƒ‰‡ ‡– ˆ‹ƒŽ‡‡– — ƒ’–‡—” „ƒ•±‡ •—” Žƒ –‡ Š‹“—‡ †‡• ‘Ž›°”‡•  ‡’”‡‹–‡ ‘Ž± —Žƒ‹”‡ǡ ‡––‡ ’”‘–‘ ‘Ž‡ ƒ ±–± ƒ’’Ž‹“—± ’‘—” Žƒ †±–‡ –‹‘ †̵‡š’Ž‘•‹ˆ•ǡ †‡• ±†‹ ƒ‡–•ǡ†‡•Š‘”‘‡•‡–Ž‡•’‡•–‹ ‹†‡•Ǥ  MotsǦclésǣ ƒ’–‡—”±Ž‡ –”‘ Š‹‹“—‡ǡ‹—‘ ƒ’–‡—”ǡƒ’–ƒ°”‡•ǡ‘Ž›°”‡• ‡’”‡‹–‡ ‘Ž± —Žƒ‹”‡ǡ „‹‘ƒ”“—‡—” †— ƒ ‡”ǡ •± —”‹–± ƒŽ‹‡–ƒ‹”‡ǡ ‘–”ØŽ‡ †‡ Ž̵‡˜‹”‘‡‡–ǡƒƒŽ›•‡•„‹‘±†‹ ƒŽ‡•Ǥ    .

(9)  ͸ . AncaftefanaFlorea. 

(10)  ‡ ƒ‰Žƒ‹•ǣ Electrochemical affinity sensors for biomedical, food andenvironmentalapplications ‡ƒ‰Žƒ‹•ǣ Ž‡ –”‘ Š‡‹ ƒŽ •‡•‘”• ’”‘˜‹†‡ ”‡Ž‹ƒ„Ž‡ ƒ† ‹‡š’‡•‹˜‡ –‘‘Ž• ˆ‘” –Š‡ †‡–‡”‹ƒ–‹‘ ‘ˆ „‹‘Ž‘‰‹ ƒŽ ƒ† Š‡‹ ƒŽ ‘’‘—†• ™‹–Š Š‹‰Š •‡•‹–‹˜‹–› ƒ† •‡Ž‡ –‹˜‹–›ǡ‹–Š‡ˆ‹‡Ž†•‘ˆ Ž‹‹ ƒŽ†‹ƒ‰‘•‹•ǡ‡˜‹”‘‡–’”‘–‡ –‹‘ƒ†ˆ‘‘†‹†—•–”›Ǥ

(11) —‘•‡•‘”• Š‘Ž† ’ƒ”–‹ —Žƒ” ’”‘‹•‡ǡ ‘„‹‹‰ –Š‡ Š‹‰Š •’‡ ‹ˆ‹ ‹–› ‘ˆ ‹—‘Ǧ ”‡ƒ –‹‘•™‹–Š–Š‡•‡•‹–‹˜‹–›‘ˆ‡Ž‡ –”‘ Š‡‹ ƒŽ‡–Š‘†•Ǥ”–‹ˆ‹ ‹ƒŽ”‡ ‡’–‘”•„ƒ•‡†‘ ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡† –‡ Š‹“—‡ ƒ––”ƒ –‡† ‘•‹†‡”ƒ„Ž‡ ƒ––‡–‹‘ ‹ „‹‘ƒƒŽ›–‹ ƒŽ • ‹‡ ‡• †—‡ –‘ ‹Š‡”‡– ƒ†˜ƒ–ƒ‰‡• ‘˜‡” ƒ–—”ƒŽ ”‡ ‡’–‘”•ǡ •— Š ƒ• Š‹‰Š •–ƒ„‹Ž‹–› ‹ Šƒ”•Š ‘†‹–‹‘•ƒ†ˆ”‡‡†‘‘ˆ‘Ž‡ —Žƒ”†‡•‹‰–‘™ƒ”†•ƒ™‹†‡”ƒ‰‡‘ˆ‘Ž‡ —Ž‡•Ǥ Š‡ ƒ‹ ‘ˆ –Š‡ –Š‡•‹• ’”‡•‡–‡† Š‡”‡ ™ƒ• –‘ †‡˜‡Ž‘’ ‡Ž‡ –”‘ Š‡‹ ƒŽ ƒˆˆ‹‹–› •‡•‘”• „ƒ•‡† ‘ ˜ƒ”‹‘—• ”‡ ‘‰‹–‹‘ ”‡ ‡’–‘”• ˆ‘” ‡˜‹”‘‡– ‘‹–‘”‹‰ǡ ˆ‘‘† •ƒˆ‡–›ƒ†„‹‘‡†‹ ƒŽˆ‹‡Ž†Ǥ Š‡ ˆ‹”•– ’ƒ”– ‘ˆ –Š‡ –Š‡•‹• ”‡˜‹‡™• –Š‡ —””‡– •–ƒ–‡ ‘ˆ ‘™Ž‡†‰‡ ‹ –Š‡•‡ ˆ‹‡Ž†•Ǥ ‡‡”ƒŽ ƒ•’‡ –• ‘ˆ ‡Ž‡ –”‘ Š‡‹ ƒŽ ‹—‘Ǧ ƒ† ƒ’–ƒǦ•‡•‘”• ƒ”‡ ’”‡•‡–‡† Š‡”‡‹ǡ –‘‰‡–Š‡” ™‹–Š •‡˜‡”ƒŽ ‡šƒ’Ž‡• ”‡’‘”–‡† ‹ –Š‡ Ž‹–‡”ƒ–—”‡ ˆ‘” –Š‡ †‡–‡ –‹‘ ‘ˆ ƒ ‡”„‹‘ƒ”‡”•ǤŠ‡ƒ†˜ƒ–ƒ‰‡•‘ˆ‹–‡‰”ƒ–‹‰ƒ‘ƒ–‡”‹ƒŽ•‹•‡•‹‰†‡˜‹ ‡•ƒ”‡ –Š‡ ’”‡•‡–‡†Ǥ – Žƒ•–ǡ •‡˜‡”ƒŽ ƒ•’‡ –• ‘ˆ –Š‡ ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡† ’‘Ž›‡”• ƒ”‡ ‹–”‘†— ‡†Ǥ Š‡’‡”•‘ƒŽ ‘–”‹„—–‹‘’ƒ”–‹••–”— –—”‡†‹–Š”‡‡ Šƒ’–‡”•ǡ–Šƒ–‹ Ž—†‡–Š‡ ‡–Š‘†‘Ž‘‰›ƒ†”‡•—Ž–•‘„–ƒ‹‡†ˆ‘”–Š‡†‡˜‡Ž‘’‡–‘ˆ„‹‘•‡•‘”•ˆ‘”–Š‡†‡–‡ –‹‘ ‘ˆ — ‹ͳ –—‘” ƒ”‡”ǡ –Š‡ ˆ‹”•– Šƒ’–‡” „‡‹‰ ˆ‘ —•‡† ‘ „‹‘ƒ••ƒ›• „ƒ•‡† ‘ ƒ‰‡–‹  „‡ƒ†• ƒ† •‡ ‘† Šƒ’–‡” ‘ ƒ Žƒ„‡ŽǦˆ”‡‡ ƒ’–ƒ•‡•‘” „ƒ•‡† ‘ ‰‘Ž† ƒ‘’ƒ”–‹ Ž‡•ǡ ƒ† ˆ‹ƒŽŽ›ǡ ƒ –Š‹”† Šƒ’–‡” †‡†‹ ƒ–‡† –‘ –Š‡ ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡†Ǧ „ƒ•‡†•‡•‘”•ˆ‘”–Š‡†‡–‡ –‹‘‘ˆ‡š’Ž‘•‹˜‡•ǡ†”—‰•ǡŠ‘”‘‡•ƒ†’‡•–‹ ‹†‡•Ǥ  Keywordsǣ ‡Ž‡ –”‘ Š‡‹ ƒŽ •‡•‘”ǡ ‹—‘•‡•‘”ǡ ƒ’–ƒ•‡•‘”ǡ ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡†’‘Ž›‡”•ǡ ƒ ‡”„‹‘ƒ”‡”ǡˆ‘‘†•ƒˆ‡–›ǡ‡˜‹”‘‡–ƒŽ ‘–”‘Žǡ„‹‘‡†‹ ƒŽ ƒƒŽ›•‹•Ǥ . .   .  .

(12) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ͹ . Résumésubstantiel  ‡• –‡ Š‹“—‡• ±Ž‡ –”‘ Š‹‹“—‡• ’‡—˜‡– ˆ‘—”‹” — ‘—–‹Ž ’‡— ‘ð–‡—š ‡– •‡•‹„Ž‡ ’‘—” Ž‡ †±˜‡Ž‘’’‡‡– †‡ ’‡–‹–• †‹•’‘•‹–‹ˆ• ’‘”–ƒ„Ž‡• “—‹ •‘– ƒ’ƒ„Ž‡• †‡ †±–‡ –‡””ƒ’‹†‡‡–†‡• ‘’‘•±•„‹‘Ž‘‰‹“—‡•‡– Š‹‹“—‡•ƒ˜‡ †‡Šƒ—–‡••‡•‹„‹Ž‹–± ‡– •’± ‹ˆ‹ ‹–±Ǥ ‡• ƒ’–‡—”• ±Ž‡ –”‘ Š‹‹“—‡• ’‡—˜‡– ²–”‡ ƒ’’Ž‹“—±• †ƒ• †‹ˆˆ±”‡–• †‘ƒ‹‡•ǡ› ‘’”‹•Ž‡†‹ƒ‰‘•–‹ ’”± ‘ ‡†‡•ƒŽƒ†‹‡•ǡŽ‡ ‘–”‘Ž†‡•±†‹ ƒ‡–•‡– Žƒ †±–‡ –‹‘ ”ƒ’‹†‡ ‡– ’”± ‹•‡ †‡• ’‘ŽŽ—ƒ–• †‡ Ž̵‡˜‹”‘‡‡– ‡– †‡• ‘–ƒ‹ƒ–• ƒŽ‹‡–ƒ‹”‡•Ǥ  ‘„Œ‡ –‹ˆ †‡ ‡ –”ƒ˜ƒ‹Ž ƒ ±–± †‡ †±˜‡Ž‘’’‡” †‡• †‹•’‘•‹–‹ˆ• †‡ †‹ƒ‰‘•–‹  ±Ž‡ –”‘ Š‹‹“—‡•’‘—”Žƒ†±–‡ –‹‘’”± ‘ ‡†— ƒ ‡”Ǥ‡„‹‘ƒ”“—‡—”–—‘”ƒŽͳ ƒ±–± Š‘‹•‹ ‘‡‘Ž± —Ž‡‘†°Ž‡‡–†‡•ƒ–‹ ‘”’•‡–†‡•ƒ’–ƒ°”‡•‘–±–±—–‹Ž‹•±• ‘‡ ±Ž±‡–• †‡ „‹‘”‡ ‘ƒ‹••ƒ ‡Ǥ ‡• ƒ‘ƒ–±”‹ƒ—š ‘– ±–± ‹–±‰”±• †ƒ• Ž‡• ƒ’–‡—”•’”‘’‘•±• ‘‡’Žƒ–‡•Ǧˆ‘”‡•†̵‹‘„‹Ž‹•ƒ–‹‘Ǥ‡•’ƒ”–‹ —Ž‡•ƒ‰±–‹“—‡• ƒ˜‡ ’”‘–±‹‡ ‡–†‡•’ƒ”–‹ —Ž‡•ƒ‰±–‹“—‡•ƒ˜‡ •–”‡’–ƒ˜‹†‹‡‘–±–±—–‹Ž‹•±‡•’‘—” —‡ ƒƒŽ›•‡ †‡ –›’‡ •ƒ†™‹ Š †̵ƒ–‹ ‘”’• ‡– †ǯƒ’–ƒ°”‡ǡ ”‡•’‡ –‹˜‡‡–Ǥ ‡• ƒ‘’ƒ”–‹ —Ž‡•†̵‘”‘–±–±—–‹Ž‹•±‡•’‘—”Ž̵‹‘„‹Ž‹•ƒ–‹‘†‡•ƒ’–ƒ°”‡•–Š‹‘Ž±•‘ ƒ”“—±••’± ‹ˆ‹“—‡•’‘—”ͳǤ ƒ –‡ Š‹“—‡ †‡• ’‘Ž›°”‡•  ‡’”‡‹–‡ ‘Ž± —Žƒ‹”‡ ‡•– —‡ ±–Š‘†‡ ˜‡”•ƒ–‹Ž‡’‘—”Žƒ•›–Š°•‡†‡”± ‡’–‡—”•ƒ”–‹ˆ‹ ‹‡Ž•ǡ•—”‘–ƒ– ‡”–ƒ‹•‹ ‘˜±‹‡–• Ž‘”•†‡Ž̵—–‹Ž‹•ƒ–‹‘†‡•ƒ–‹ ‘”’•‘—†‡•ƒ’–ƒ°”‡•Ǥƒ—–”‡‘„Œ‡ –‹ˆ†‡ ‡–”ƒ˜ƒ‹Žƒ±–± Ž‡ †±˜‡Ž‘’’‡‡– †‡ ƒ’–‡—”• ±Ž‡ –”‘ Š‹‹“—‡•  ‡’”‡‹–‡• ‘Ž± —Žƒ‹”‡• ’‘—” Žƒ †±–‡ –‹‘ †‡ ±†‹ ƒ‡–•ǡ †‡ ’‘ŽŽ—ƒ–• †‡ Ž̵‡˜‹”‘‡‡– ‡– †‡ ‘–ƒ‹ƒ–• ƒŽ‹‡–ƒ‹”‡•Ǥ ‘—• ƒ˜‘• Š‡” Š±  †±˜‡Ž‘’’‡” — ’”‘–‘ ‘Ž‡ ‰±±”‹“—‡ “—‹ ’‘—””ƒ‹– ²–”‡ ƒ’’Ž‹“—±  —‡ Žƒ”‰‡ ‰ƒ‡ †‡ ‘Ž± —Ž‡•ǡ › ‘’”‹• Ž‡• ‘’‘•±• ‘ ±Ž‡ –”‘ƒ –‹ˆ•ǡ ‡ —–‹Ž‹•ƒ– ‘‡ ±†‹ƒ–‡—” ”‡†‘š Ž‡ ‘—’Ž‡ Š‡šƒ ›ƒ‘ˆ‡””‹–‡ Ȁ Š‡šƒ ›ƒ‘ˆ‡””ƒ–‡Ǥ‡•ˆ‹Ž•‹’”‹±•‘–±–±’”±’ƒ”±‡•’ƒ”±Ž‡ –”‘’‘Ž›±”‹•ƒ–‹‘’ƒ” ˜‘Ž–ƒ±–”‹‡ › Ž‹“—‡ †‡ ƒ‘’ƒ”–‹ —Ž‡• ˆ‘ –‹‘ƒŽ‹•±‡• ƒ˜‡  pǦƒ‹‘–Š‹‘’Š±‘Ž ‡ ’”±•‡ ‡†‡‘Ž± —Ž‡•†‡Žƒ•—„•–ƒ ‡‘†°Ž‡Ǥ̵‡š–”ƒ –‹‘—Ž–±”‹‡—”‡†‡Žƒ•—„•–ƒ ‡ ‘†°Ž‡ ‘†—‹–  Žƒ ˆ‘”ƒ–‹‘ †‡ ƒ˜‹–±• ƒ’ƒ„Ž‡• †‡ ”‡ ‘ƒ‹••ƒ ‡ •’± ‹ˆ‹“—‡ǡ “—‹ •‘– ƒ’ƒ„Ž‡•†‡Ž‹‡”Ž‡•ƒƒŽ›–‡•Ǥ ‘—• ƒ˜‘• ‹˜‡•–‹‰—± Ž̵ƒ’’Ž‹ ƒ–‹‘ ’”ƒ–‹“—‡ †‡• ƒ’–‡—”• ’”‘’‘•±• ’ƒ” Ž̵ƒƒŽ›•‡ †‡ƒ–”‹ ‡• ‘’Ž‡š‡•“—‹ ‘–‹‡‡– Ž̵ƒƒŽ›–‡ǡ ‘‡Žǯ‡ƒ— †— ”‘„‹‡– ‡– Ž̵‡ƒ—†‡Žƒ”‹˜‹°”‡ǡŽ‡‹‡ŽǡŽ‡•±”—‡–Ž‡•ˆ‘”—Žƒ–‹‘•†‡±†‹ ƒ‡–•Ǥ ‡ ’”‡‹‡” Šƒ’‹–”‡ †‡ Žƒ ‘–”‹„—–‹‘ ’‡”•‘‡ŽŽ‡ ’”±•‡–‡ — „‹‘Ǧ‡••ƒ‹• ‘’–‹‹•±•’‘—”Žƒ†±–‡ –‹‘†‡Žƒ— ‹‡ͳ†ƒ•†‡•± Šƒ–‹ŽŽ‘•†‡•±”—Ǥ.

(13)  ͺ . AncaftefanaFlorea. ͳ ‡•– —‡ ‰Ž› ‘’”‘–±‹‡ –”ƒ•‡„”ƒƒ‹”‡ ‡š’”‹±‡ •—” Žƒ •—”ˆƒ ‡ ƒ’‹ ƒŽ‡†‡†‹ˆˆ±”‡–‡• ‡ŽŽ—Ž‡•±’‹–Š±Ž‹ƒŽ‡•ǡ“—‹‡•–•—”‡š’”‹±‡†ƒ•Ž‡•ƒ‰†ƒ•Ž‡ ƒ• †‡• ’”‘ ‡••—• ±‘’Žƒ•‹“—‡•Ǥ ƒ” ‘•±“—‡–ǡ Žƒ ͳ ’‡—– ²–”‡ —–‹Ž‹•±‡ ‘‡ ƒ”“—‡—” –—‘”ƒŽ ’‘–‡–‹‡Ž ’‘—” ±–ƒ„Ž‹” Ž‡ †‹ƒ‰‘•–‹  ‡– Ž‡ ’”‘‘•–‹  †ƒ• ’Ž—•‹‡—”• –›’‡•†‡ ƒ ‡”Ǥ ‡––‡ ±–—†‡ ’”±•‡–‡ †‡—š ƒ’’”‘ Š‡• †‹ˆˆ±”‡–‡• ’‘—” Žƒ †±–‡ –‹‘ †— ƒ”“—‡—” –—‘”ƒŽ ͳ †ƒ• — ˆ‘”ƒ– •ƒ†™‹ Š ‡ —–‹Ž‹•ƒ– †‡• ’ƒ”–‹ —Ž‡• ƒ‰±–‹“—‡• ‘‡ •—’’‘”– •‘Ž‹†‡ ‡– †‡• ƒ–‹ ‘”’• ‘— †‡• ƒ’–ƒ°”‡• ‘‡ ‘Ž± —Ž‡• †‡ „‹‘”‡ ‘ƒ‹••ƒ ‡Ǥ ‡• ƒ’–ƒ°”‡• —–‹Ž‹•±• †ƒ• ‡ –”ƒ˜ƒ‹Ž ‘– ±–± •±Ž‡ –‹‘±•†̵—‡„‹„Ž‹‘–Š°“—‡†̵ƒ’–ƒ°”‡•ǡ ‘­—’ƒ”ǡ“—‹‘–Žƒ ƒ’ƒ ‹–±†‡ ”‡ ‘ƒÁ–”‡Žƒ’”‘–±‹‡ͳǤ ƒ ‘Ž± —Ž‡ ‹„Ž‡ ‡•– ƒ’–—”±‡ ‡–”‡ Ž̵ƒ–‹ ‘”’• ’”‹ƒ‹”‡ ‘— Ž̵ƒ’–ƒ°”‡ ‹‘„‹Ž‹•±•—”†‡•’ƒ”–‹ —Ž‡•ƒ‰±–‹“—‡•‡–—ƒ–‹ ‘”’•‘—ƒ’–ƒ°”‡•‡ ‘†ƒ‹”‡Ǥƒ ”±ƒ –‹‘ †̵ƒˆˆ‹‹–± ‡•– ƒ”“—±‡ ƒ˜‡  Žƒ ’Š‘•’Šƒ–ƒ•‡ ƒŽ ƒŽ‹‡ †ƒ• †‡• †‹ˆˆ±”‡–‡• ‘ˆ‹‰—”ƒ–‹‘• †̵‡••ƒ‹Ǥ ‘—–‡• Ž‡• ˜ƒ”‹ƒ„Ž‡• ‘ ‡”ƒ– Ž‡• „‹‘Ǧ‡••ƒ‹• ‘– ±–± ‘’–‹‹•±‡•Ǥ ƒ —Ž–‹†±–‡ –‹‘ ±Ž‡ –”‘ Š‹‹“—‡ ‡•– ”±ƒŽ‹•±‡ ’ƒ” ˜‘Ž–ƒ±–”‹‡ ’—Ž•‡ †‹ˆˆ±”‡–‹‡ŽŽ‡ȋȌǡ‡—–‹Ž‹•ƒ–Š—‹– ‡ŽŽ—Ž‡•‹’”‹±‡••±”‹‰”ƒ’Š‹“—‡•ǡ’ƒ”Ž̵ƒ††‹–‹‘ †— •—„•–”ƒ– ‡œ›ƒ–‹“—‡ ȋͳǦƒ’Š–›Ž‡ ’Š‘•’Šƒ–‡Ȍ ‡– •ƒ ‘˜‡”•‹‘ —Ž–±”‹‡—”‡ ‡ ͳǦ ƒ’Š–‘Žǡ — ‘’‘•± ±Ž‡ –”‘ƒ –‹ˆǤ ‘—– †̵ƒ„‘”†ǡ ‘—• ƒ˜‘• ‘’–‹‹•± ’Ž—•‹‡—”• ’ƒ”ƒ°–”‡•‡š’±”‹‡–ƒ—š“—‹‹ˆŽ—‡ ‡–Žƒ’‡”ˆ‘”ƒ ‡†‡•„‹‘Ǧ‡••ƒ‹•Ǥ•—‹–‡ǡŽ‡• ’‡”ˆ‘”ƒ ‡•ƒƒŽ›–‹“—‡•‘„–‡—‡•†ƒ•†‡• ‘†‹–‹‘•‘’–‹‹•±‡•†‡•†‡—š ƒ’–‡—”• †±˜‡Ž‘’’±•‘–±–± ‘’ƒ”±‡•‡–‡”‡•†‡•‡•‹„‹Ž‹–±‡–†‡•±Ž‡ –‹˜‹–±ƒˆ‹†‡ Š‘‹•‹” Žƒ‡‹ŽŽ‡—”‡±–Š‘†‡’‘—”ƒƒŽ›•‡”Ž‡•± Šƒ–‹ŽŽ‘•†‡•±”—†‡ ƒ ‡”Ǥ‡†‘•ƒ‰‡ „ƒ•‡†̵ƒ’–ƒ°”‡‡˜‹•ƒ‰±‡†—ƒ‘–”±—‡‡‹ŽŽ‡—”‡•‡•‹„‹Ž‹–±‡–•±Ž‡ –‹˜‹–±’‘—”Žƒ †±–‡ –‹‘†‡„‹‘ƒ”“—‡—”’‘—” ƒ ‡”ͳ’ƒ””ƒ’’‘”–ƒ—†‘•ƒ‰‡„ƒ•‡†̵ƒ–‹ ‘”’•Ǥ ƒ• †‡• ‘†‹–‹‘• ‘’–‹‹•±‡•ǡ —‡ ‘—”„‡ †̵±–ƒŽ‘ƒ‰‡ Ž‹±ƒ‹”‡ ’‘—” †‡• •‘Ž—–‹‘• –ƒ’‘†‡ͳƒ±–±‘„–‡—‡†ƒ•—‹–‡”˜ƒŽŽ‡†‡ͲͳͲ‰Ȁƒ˜‡ —‡Ž‹‹–‡†‡ †±–‡ –‹‘ȋα͵„ŽƒȀ’‡–‡Ȍ†‡ͳǡͶ‰Ȁȋ ‘””‡•’‘†ƒ–Žǯ‹–‡”˜ƒŽŽ‡†‡ͲͲǡʹͺ ǡ  †‡ ͲǡͲ͵͹ Ȍǡ „‹‡ ‡ †‡••‘—• †‡• Ž‹‹–‡• †‡ †±–‡ –‹‘ ”ƒ’’‘”–±‡• ’‘—” †̵ƒ—–”‡• ƒ’–ƒ•‡•‘”• ’”±•‡–• †ƒ• Žƒ Ž‹––±”ƒ–—”‡Ǥ ˆ‹ †̵±˜ƒŽ—‡” Žǯƒ’’Ž‹ ƒ„‹Ž‹–± †‡ Žǯƒ’–ƒ•‡•‘”†±˜‡Ž‘’’±‡–†̵±˜ƒŽ—‡”Ž̵‹ˆŽ—‡ ‡†‡Ž̵‡ˆˆ‡–†‡Žƒƒ–”‹ ‡ǡ†‡•± Šƒ–‹ŽŽ‘• †‡ •±”— ‘ ’ƒ–Š‘Ž‘‰‹“—‡• †‘’±• ƒ˜‡  †‹ˆˆ±”‡–‡• ‘ ‡–”ƒ–‹‘• ‘—‡• †‡ Žƒ ’”‘–±‹‡ ͳ ‘– ±–± ƒ—••‹ ƒƒŽ›•±•Ǥ ‡ Ž‹‹–‡ †‡ †±–‡ –‹‘†‡ ͵ǡͲ ‰ Ȁ  ‡–—‡ Ž‹‹–‡†‡“—ƒ–‹ˆ‹ ƒ–‹‘ȋαͳͲ„ŽƒȀ’‡–‡Ȍ†‡ͳͲǡͲ‰Ȁ‘–±–±‘„–‡—•Ǥ‡’Ž—•ǡ ‘—• ƒ˜‘• †±–‡”‹± —‡ ‘””±Žƒ–‹‘ •‡‹Ǧ“—ƒ–‹–ƒ–‹˜‡ ‡–”‡ Žƒ ‘ ‡–”ƒ–‹‘ †‡ ͳ–”‘—˜±‡†ƒ•†‡•± Šƒ–‹ŽŽ‘•†‡•±”—•†‡’ƒ–‹‡–•ƒ˜‡  ƒ ‡”‡–†—•–ƒ†‡†‡ ƒŽ‹‰‹–±‘„–‡—’ƒ”Ž‡†‹ƒ‰‘•–‹ ‹—‘Š‹•–‘ Š‹‹“—‡ǡ†±‘–”ƒ–Ž‡•ƒ’’Ž‹ ƒ–‹‘• ’‘–‡–‹‡ŽŽ‡•’‘—”Ž‡†±’‹•–ƒ‰‡†— ƒ ‡”Ǥ.

(14) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ͻ . ‡ †‡—š‹°‡ Šƒ’‹–”‡ ’”±•‡–‡ — ƒ’–ƒ•‡•‘” •ƒ• ƒ”“—ƒ‰‡ „ƒ•± •—” Žǯ±Ž‡ –”‘†±’‘•‹–‹‘ †‡ ƒ‘’ƒ”–‹ —Ž‡• †̵‘” •—” †‡• ±Ž‡ –”‘†‡• ‹’”‹±‡• •±”‹‰”ƒ’Š‹“—‡‡–  ’‘—” Žƒ †±–‡ –‹‘ †— ƒ”“—‡—” –—‘”ƒŽ ͳǤ ƒ• Žƒ ’”‡‹°”‡ ±–ƒ’‡ǡŽƒ•—”ˆƒ ‡†‡•±Ž‡ –”‘†‡•‡‰”ƒ’Š‹–‡‡•–‘†‹ˆ‹±‡’ƒ”±Ž‡ –”‘†±’‘•‹–‹‘ƒ˜‡ †‡• ƒ‘’ƒ”–‹ —Ž‡• †̵‘”Ǥ •—‹–‡ǡ Ž‡• ƒ’–ƒ°”‡• •’± ‹ˆ‹“—‡• ’‘—” Ž̵ƒ–‹‰°‡ ͳ ‘– ±–± ƒ—–‘Ǧƒ••‡„Ž±••—”Žƒ•—”ˆƒ ‡†̵‘”Ǥ̵‹–‡”ƒ –‹‘‡–”‡Ž̵ƒ’–ƒ°”‡‡–Žƒ’”‘–±‹‡ͳ ƒ ±–± ±–—†‹±‡ ’ƒ” Žƒ –‡ Š‹“—‡ †‡ •’‡ –”‘• ‘’‹‡ ±Ž‡ –”‘ Š‹‹“—‡ †̵‹’±†ƒ ‡ ’ƒ” Žƒ ˜ƒ”‹ƒ–‹‘†‡Žƒ”±•‹•–ƒ ‡†‡–”ƒ•ˆ‡”–†‡ Šƒ”‰‡Ǥ‡ƒ—‰‡–ƒ–‹‘†‡Žƒ”±•‹•–ƒ ‡†‡ –”ƒ•ˆ‡”– †‡ Šƒ”‰‡ ƒ ±–± ‘„•‡”˜±‡ ƒ’”°• Ž̵‹‘„‹Ž‹•ƒ–‹‘ †‡• ƒ’–ƒ°”‡• ‡– †‡• ’”‘–±‹‡•  Žƒ •—”ˆƒ ‡ †— ƒ’–‡—”Ǥ ‡• ”±•—Ž–ƒ–• †±‘–”‡– “—‡ Žƒ ±–Š‘†‡ ±Ž‡ –”‘ Š‹‹“—‡—–‹Ž‹•ƒ–—‡•‘†‡†̵ƒ’–ƒ°”‡•‡•–•‹’Ž‡‡– ‘‘†‡ǡ‡–’‡”‡–Žƒ †±–‡ –‹‘ “—ƒ–‹–ƒ–‹˜‡ †‡ Žƒ ’”‘–±‹‡ ͳ Š—ƒ‹‡Ǥ ƒ ‘—”„‡ †̵±–ƒŽ‘ƒ‰‡ ’‘—” Žƒ †±–‡”‹ƒ–‹‘†‡Žƒ’”‘–±‹‡ͳƒ±–±‘„–‡—‡†ƒ•†‡• ‘†‹–‹‘•‘’–‹‹•±‡•Ǥƒ Ž‹‹–‡ †‡ †±–‡ –‹‘ ‡•–‹±‡†‡ Žƒ ’”‘–±‹‡ ͳ ƒ ±–±†‡ ͵ǡ͸ ‰Ȁ †ƒ• Žǯ‹–‡”˜ƒŽŽ‡ Ž‹±ƒ‹”‡†‡ʹǤͷǦͳͷ‰ȀǤ ˆ‹ǡ Ž‡ †‡”‹‡” Šƒ’‹–”‡ ’”±•‡–‡ Ž‡ †±˜‡Ž‘’’‡‡– †‡ 

(15) Ǧ ƒ’–‡—”• ±Ž‡ –”‘ Š‹‹“—‡• ’‘—” Žƒ †±–‡ –‹‘ •‡•‹„Ž‡ ‡– •±Ž‡ –‹˜‡ †‡ †‹ˆˆ±”‡–• ƒƒŽ›–‡• ‹„Ž‡•Ǥ ‘—•ƒ˜‘• Š‡” Š±†±˜‡Ž‘’’‡”—’”‘–‘ ‘Ž‡‰±±”‹“—‡•—”Žƒ„ƒ•‡†ǯ—‡‡„”ƒ‡ Š›„”‹†‡†‡’‘Ž›°”‡‡’”‡‹–‡•‘Ž± —Žƒ‹”‡•Ȁ—•“—‹’‡—–²–”‡ƒ’’Ž‹“—±‡—‡ Žƒ”‰‡‰ƒ‡†‡‘Ž± —Ž‡•±Ž‡ –”‘ƒ –‹˜‡•‡–‘±Ž‡ –”‘ƒ –‹˜‡•ǤǡŽƒ‰‡ ‹–ƒ„‹‡ǡŽƒ –±–”ƒ › Ž‹‡ǡ Ž̵‡•–”ƒ†‹‘Ž ‡– Ž‡ ‰Ž›’Š‘•ƒ–‡ ‘– ±–± ±–—†‹±• ‘‡ ‘Ž± —Ž‡• ‘†°Ž‡•Ǥ ‘—–†̵ƒ„‘”†ǡ—‡‘‘ ‘— Š‡†̵ƒ—–‘Ǧƒ••‡„Žƒ‰‡†‡‡•–ˆ‘”±‡Žƒ•—”ˆƒ ‡†‡ Ž̵±Ž‡ –”‘†‡†ǯ‘”’ƒ”†‡•Ž‹ƒ‹•‘•—ǦǤ•—‹–‡ǡŽ‡ˆ‹Ž

(16) ƒ±–±†±’‘•±•—”Ž̵±Ž‡ –”‘†‡ ’ƒ” ±Ž‡ –”‘’‘Ž›±”‹•ƒ–‹‘ †— ‰”‘—’‡‡– ƒ‹Ž‹‡ †‡  ‰”‡ˆˆ±• •—” †‡• ±Ž‡ –”‘†‡• †ǯ‘” ‡– •—” —•Ǥ ˆ‹ †̵‘„–‡‹” †‡• ˆ‹Ž• ‹’”‹±•ǡ Ž‡ ’”‘ ‡••—• †̵±Ž‡ –”‘’‘Ž›±”‹•ƒ–‹‘ƒ±–±”±ƒŽ‹•±‡’”±•‡ ‡†‡‘Ž± —Ž‡•‘†°Ž‡•ǡŽ̵±Ž‹‹ƒ–‹‘ •—„•±“—‡–‡ †— ‘†°Ž‡ Žƒ‹••ƒ– †‡• ƒ˜‹–±• “—‹ •‡”˜‡– †‡ •‹–‡• †‡ ”‡ ‘ƒ‹••ƒ ‡ •±Ž‡ –‹˜‡Ǥ ‘„‹ƒ– Ž‡• ƒ˜ƒ–ƒ‰‡• †‡ Ž̵‹’”‡••‹‘ ‘Ž± —Žƒ‹”‡ ‡– †‡ Žǯ±Ž‡ –”‘†±’‘•‹–‹‘ƒ˜‡  ‡—š ‘ˆ±”±•’ƒ”—•ǡŽ‡• ƒ’–‡—”•†±˜‡Ž‘’’±•’”±•‡–‡– —‡ „‘‡ •‡•‹„‹Ž‹–± ‡– —‡ ‰”ƒ†‡ •±Ž‡ –‹˜‹–±Ǥ Ž—•‹‡—”• ’ƒ”ƒ°–”‡• “—‹ ‹ˆŽ—‡ ‡– Ž‡•’‡”ˆ‘”ƒ ‡•†‡• ƒ’–‡—”•‘–±–±‘’–‹‹•±•‡–Ž‡•ƒ–±”‹ƒ—š†‡†±–‡ –‹‘‘–±–± ƒ’’Ž‹“—±‡•ƒ˜‡ •— °•’‘—”Ž̵ƒƒŽ›•‡†‡•± Šƒ–‹ŽŽ‘•”±‡Ž•Ǥ.    .

(17)  ͳͲ . AncaftefanaFlorea.   LISTOFPUBLICATIONS  ͳǤ A. Floreaǡ Ǥ ƒŽ‡ƒ–ǡ Ǥ ”‹•–‡ƒǡ Ǥ ƒœŽ‘—Ǧ”†ƒƒ‹ǡ Ǥ £†—Ž‡• —ǡ ƒ„‡Ž ˆ”‡‡ͳƒ’–ƒ•‡•‘”•„ƒ•‡†‘‡Ž‡ –”‘†‡’‘•‹–‹‘‘ˆ‰‘Ž†ƒ‘’ƒ”–‹ Ž‡•‘ • ”‡‡ ’”‹–‡† ‡Ž‡ –”‘†‡•ǡ Ž‡ –”‘ Š‡‹•–”› ‘—‹ ƒ–‹‘•ǡ ͵͵ ȋʹͲͳ͵Ȍ ͳʹ͹Ǧͳ͵ͲǡISIImpactFactor4.287 ʹǤ A.Florea,Ǥ”‹•–‡ƒǡǤ †—Ž‡• —ǡͳ–—‘”ƒ”‡”ˆ‘”–Š‡†‡–‡ –‹‘‘ˆ ‘˜ƒ”‹ƒ ƒ ‡”Ǥ  ‹‹”‡˜‹‡™ǡ ƒ”ƒ ‹ƒ 

(18)

(19) ǡ ͳ ȋʹͲͳͶȌ  ͳǦͳ͵ǡ ISI Impact Factor0.971 ͵Ǥ ǤǤ —‘ǡA.FloreaǡǤ”‹•–‡ƒǡ Ǥ‡••—‡‹ŽŽ‡ǡ Ǥ‘ ƒ•‘ǡ Ǥ ‘—–ƒŽƒ†ǡǤǤ Šƒ‰ǡǤ£†—Ž‡• —ǡ Ǥƒ‰ƒ”†‡ǡǤ ƒˆˆ”‡œ‹ Ǧ‡ƒ—Ž–ǡͳǡ͵ǡͷǦ”‹‹–”‘–‘Ž—‡‡ †‡–‡ –‹‘ „› ƒ ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡† ’‘Ž›‡” •‡•‘” „ƒ•‡† ‘ ‡Ž‡ –”‘’‘Ž›‡”‹œƒ–‹‘‘ˆƒ‹ ”‘’‘”‘—•Ǧ‡–ƒŽǦ‘”‰ƒ‹ ˆ”ƒ‡™‘”ǡ‡•‘”• ƒ† –—ƒ–‘”•ʹͲ͹ȋʹͲͳͷȌͻ͸ͲǦͻ͸͸ǡISIImpactFactor3.840 ͶǤ A. Floreaǡ ǤǤ —‘ǡ Ǥ ”‹•–‡ƒǡ Ǥ ‡••—‡‹ŽŽ‡ǡ Ǥ ‘ ƒ•‘ǡ Ǥ ‘—–ƒŽƒ†ǡ Ǥ œ›ƒ†‡˜› Šǡ Ǥ £†—Ž‡• —ǡ Ǥ ƒˆˆ”‡œ‹ Ǧ‡ƒ—Ž–ǡ –‹ ƒ ‡” †”—‰ †‡–‡ –‹‘ —•‹‰ƒŠ‹‰ŠŽ›•‡•‹–‹˜‡‘Ž‡ —Žƒ”Ž›‹’”‹–‡†‡Ž‡ –”‘ Š‡‹ ƒŽ•‡•‘”„ƒ•‡† ‘ ƒ ‡Ž‡ –”‘’‘Ž›‡”‹œ‡† ‹ ”‘’‘”‘—• ‡–ƒŽ ‘”‰ƒ‹  ˆ”ƒ‡™‘”ǡ ƒŽƒ–ƒǤ ͳ͵ͺȋʹͲͳͷȌ͹ͳǦ͹͸ǤISIImpactFactor3.511 ͷǤ A. Floreaǡ Ǥ ƒ˜ƒŽŽ‹ǡ Ǥ ”‹•–‡ƒǡ Ǥ £†—Ž‡• —ǡ Ǥ ƒ””ƒœœƒǡ  ‘’–‹‹œ‡† „‹‘ƒ••ƒ›ˆ‘”— ‹ͳ†‡–‡ –‹‘‹•‡”—•ƒ’Ž‡•ǡŽ‡ –”‘ƒƒŽ›•‹•Ǥʹ͹ȋʹͲͳͷȌ ͳͷͻͶǦͳ͸Ͳͳ.ISIImpactFactor2.502 ͸Ǥ Ǥ ”‹•–‡ƒǡ A. Floreaǡ Ǥ £†—Ž‡• —ǡ Ǥ ‡”–‹•Ǥ ‹‘•‡•‘”•ǡ Šƒ’–‡” 

(20)

(21) ǡ

(22) —‘•‡•‘”•Ǥ†Ǥ

(23) –‡ ŠȋʹͲͳͷȌinpress ͹Ǥ A. Floreaǡ Ǥ ”‹•–‡ƒǡ Ǥ ‘ ƒ•‘ǡ Ǥ £†—Ž‡• —ǡ Ǥ ƒˆˆ”‡œ‹ Ǧ‡ƒ—Ž–Ǥ Ž‡ –”‘ Š‡‹ ƒŽ •‡•‘” ˆ‘” –Š‡ †‡–‡ –‹‘ ‘ˆ ‡•–”ƒ†‹‘Ž „ƒ•‡† ‘ ‡Ž‡ –”‘’‘Ž›‡”‹œ‡† ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡† ’‘Ž›–Š‹‘ƒ‹Ž‹‡ ˆ‹Ž ƒ† ‰‘Ž† ƒ‘’ƒ”–‹ Ž‡• ƒ’Ž‹ˆ‹ ƒ–‹‘Ǥ Ž‡ –”‘ Š‡‹•–”› ‘—‹ ƒ–‹‘•Ǥ ͷͻ ȋʹͲͳͷȌ ͵͸Ǧ͵ͻǤISIImpactFactor4.287 ͺǤ Ǥ‘—‰”‹‹ǡ A.FloreaǡǤ”‹•–‡ƒǡǤƒ†—Ž‡• —ǡ Ǥ‘ ƒ•‘ǡǤ””ƒ Š‹†ǡǤ ‘— Š‹Š‹ǡǤŽƒ”‹ǡǤ ƒˆˆ”‡œ‹ Ǧ‡ƒ—Ž–Ǥ‡–‡ –‹‘‘ˆ–‡–”ƒ › Ž‹‡‹Š‘‡› —•‹‰ƒ‘Ž‡ —Žƒ”Ž›‹’”‹–‡†•‡•‘”Ǥ ‘‘†‘–”‘ŽǤͷͻȋʹͲͳ͸ȌͶʹͶǦͶʹͻǤISI ImpactFactor2.819.

(24) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ͳͳ .

(25)  ͳʹ . AncaftefanaFlorea.  . TableofContents . . INTRODUCTION. 18. STATEOFTHEART. 20. 1.. 21 22 23 24 25 26. Generalaspectsofaffinitysensors 1.2.Generalclassification 1.3.Voltamperometricsensors 1.4.Impedimetricsensors 1.5. Singleusesensors 1.6.Immobilizationofthebioelements. 2.. Immunosensorsandaptasensors 2.1.Definitions 2.2.Generalclassification 2.3.Typesofformat 2.3.1.Competitiveimmunosensors 2.3.2.NonͲcompetitiveimmunosensors 2.4.Typesofbiorecognitionelement 2.4.1.Antibodies 2.4.2.Aptamers 2.5.Immobilizationofantibodies/aptamers 2.5.1.Physicaladsorption 2.5.2.Entrapment 2.5.3.CovalentBinding 2.5.4.OrientedBinding 2.6.Applicationsofelectrochemicalimmunosensorsforcancerbiomarkers detection 3.. 4.. Nanomaterialsforthedesignofamperometricsensors 3.1.Magneticbeads 3.2.Goldnanoparticles Molecularlyimprintedpolymers. 28 28 29 30 30 30 32 32 34 35 35 35 36 36 38 42 43 44 45.

(26) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. 4.1.Definitionandgeneralprinciple 4.2.Classification ͶǤ͵ǤPreparationofmolecularlyimprintedpolymer• ͶǤͶǤMolecularlyimprintedpolymersinsensors PERSONALCONTRIBUTIONS. ͳ͵ . 45 46 47 48 53. 1.OptimizedbioassaysforMucin1detectioninserumsamples 55 1.1.Introduction 55 1.2.MaterialsandMethods 57 1.2.1.Chemicalsandinstrumentation 57 1.2.2.ProtocolofantibodyͲbasedbioassay 58 1.2.3.ProtocolofaptamerͲbasedbioassay 60 1.2.3.1.Immobilizationoftheprimaryaptamer 61 1.2.3.2.BlockingoffreebindingͲsites 61 1.2.3.3.CapturingtheMUC1protein 61 1.2.3.4.BindingofsecondaryaptamerandlabellingwithstreptavidinͲ alkalinephosphatase 61 1.2.4.Analysisofhumanserumsamplesbytheaptamerbasedbioassay 62 1.3.Resultsanddiscussion 62 1.3.1.OptimizationofexperimentalparametersofaptamerͲbasedbioassay  62 1.3.2.OptimizationofexperimentalparametersforantibodyͲbasedbioassay  64 1.3.3.DetectionofMUC1inbufferedsolutions 66 1.3.4.Selectivitystudiesofthebioassay 67 1.3.5.Serumsamplesanalysis 68 1.4.Conclusions 72 2.LabelfreeMUC1aptasensorbasedonelectrodepositionofgold nanoparticlesonscreenprintedelectrodes 2.1.Introduction 2.2.Experimental 2.2.1.Chemicalsandinstrumentation 2.2.2.PreparationofAuNPsmodifiedSPE 2.2.3.Immobilizationoftheaptamerandinteractionwiththeprotein 2.3.Resultsanddiscussion 2.3.1.PrincipleofelectrochemicalaptamerͲbasedbiosensor 2.3.2.Optimizationofexperimentalparameters. 74 74 75 75 76 76 77 77 77.

(27)  ͳͶ . AncaftefanaFlorea. 2.3.3.CharacterizationofAuNPsͲgraphiteSPEͲbasedaptasensorbyEIS 2.3.4.QuantitativedetectionofMUC1protein 2.4.Conclusion. 79 81 82. 3.MIPǦbasedsensorsforthedetectionofvariousanalytesof environmental,biomedicalandfoodsafetyinterest 85 3.1.Introduction 85 3.2.Materialsandmethods 90 3.2.1.Chemicalsandinstrumentation 90 3.2.2.Experimentaltechniquesusedforfabricationandcharacterizationof themolecularlyimprintedsensors 91 3.2.2.1.StepsintheconstructionoftheMIPsensors 91 3.2.2.2.PreparationofthefunctionalizedAuNPs 92 3.2.2.3.Electrodepositionofmolecularlyimprintingfilmsontothegold electrodes 93 3.2.2.4.ElectrochemicalmeasurementsonMIPandNIPͲmodified electrodes 94 3.2.2.5.Surfacecharacterizationbyatomicforcemicroscopy(AFM) 94 3.2.2.6.Analysisofrealsamples 95 3.3.Resultsanddiscussion 95 3.3.1.ElectrochemicalpreparationofMIPandNIPbasedsensors 95 3.3.2.ElectrochemicalandmorphologicalcharacterizationofMIPandNIP films 99 3.3.3.ElectrochemicalbehaviourandrecognitionabilityofMIPfilmstowards thetargetanalytes 101 3.3.4.Optimizationofexperimentalconditions 105 3.3.4.1.OptimizationofexperimentalparametersforGMTimprinted sensor 105 3.3.4.2.OptimizationofexperimentalparametersforTCimprintedsensor  108 3.3.4.3.OptimizationofexperimentalparametersforGlyimprintedfilms  109 3.3.5.AnalyticalperformanceoftheimprintedandnonͲimprintedpolymer  111 3.3.6.Analysesofrealsamples 117 3.3.7.Reproducibilityandreusabilityoftheimprintedsensor 119 3.3.8.Stabilitystudies 120 3.4.Conclusions 120.

(28) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ͳͷ . 4.Generalconclusions. 122. 5.Originalityofthethesis. 124. REFERENCES. 125. .         .

(29)  ͳ͸ . AncaftefanaFlorea. ABBREVIATIONS  Ab Ag Apt AP A(n) BSA CE cDNA CDR CNT CV DEA DNA DNT DPV DPSV dT E2 EDTA EIS ELISA GC GC/MS GCE Gly GMT HPLC Ig LBL LOD LOQ LSV. –‹„‘†› –‹‰‡ ’–ƒ‡” ŽƒŽ‹‡’Š‘•’Šƒ–ƒ•‡ †‡‹‡— Ž‡‘–‹†‡ ‘˜‹•‡”—ƒŽ„—‹ ‘—–‡”‡Ž‡ –”‘†‡ ‘’Ž‡‡–ƒ”›†‡‘š›”‹„‘— Ž‡‹ ƒ ‹† ‘’Ž‡‡–ƒ”›†‡–‡”‹‹‰”‡‰‹‘ ƒ”„‘ƒ‘–—„‡• › Ž‹ ˜‘Ž–ƒ‡–”› ‹‡–Š›Ž‡‡ƒ‹‡ ‡‘š›”‹„‘— Ž‡‹ ƒ ‹† ‹‹–”‘–‘Ž—‡‡ ‹ˆˆ‡”‡–‹ƒŽ’—Ž•‡ ˜‘Ž–ƒ‡–”› ‹ˆˆ‡”‡–‹ƒŽ’—Ž•‡•–”‹’’‹‰˜‘Ž–ƒ‡–”› ‡‘š›–›‹‡ •–”ƒ†‹‘Ž Š›Ž‡‡†‹ƒ‹‡–‡–”ƒƒ ‡–‹ ƒ ‹† Ž‡ –”‘ Š‡‹ ƒŽ‹’‡†ƒ ‡•’‡ –”‘• ‘’› œ›‡ǦŽ‹‡†‹—‘•‘”„‡–ƒ••ƒ›. ƒ•Š”‘ƒ–‘‰”ƒ’Š›. ƒ• Š”‘ƒ–‘‰”ƒ’Š›ƒ•••’‡ –”‘‡–”›. Žƒ••› ƒ”„‘‡Ž‡ –”‘†‡. Ž›’Š‘•ƒ–‡. ‡ ‹–ƒ„‹‡ ‹‰Š‡”ˆ‘”ƒ ‡‹“—‹†Š”‘ƒ–‘‰”ƒ’Š›

(30) —‘‰Ž‘„—Ž‹ ƒ›‡”„›Žƒ›‡” ‹‹–‘ˆ†‡–‡ –‹‘ ‹‹–‘ˆ“—ƒ–‹ˆ‹ ƒ–‹‘ ‹‡ƒ”•™‡‡’ ˜‘Ž–ƒ‡–”›.

(31) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. LR mAb MUC1 MUC4 MUC16 MIP MMOF mRNA MW NIP ODN pAb PATP PCR rAb RE RNA SAMs SCE SEM SPE SPCs SPR SWV TC TNT TRIS WE WHO QD QCM. ‹‡ƒ””ƒ‰‡ ‘‘ Ž‘ƒŽƒ–‹„‘†› — ‹ͳ — ‹Ͷ — ‹ͳ͸ ‘Ž‡ Ž—Žƒ”Ž›‹’”‹–‡†’‘Ž›‡” ‹ ”‘’‘”‘—•‡–ƒŽǦ‘”‰ƒ‹ ˆ”ƒ‡™‘” ‹ ”‘Ǧ”‹„‘— Ž‡‹ ƒ ‹† ‘Ž‡ —Žƒ”™‡‹‰Š– ‘Ǧ‹’”‹–‡†’‘Ž›‡” Ž‹‰‘†‡‘š›— Ž‡‘–‹†‡ ‘Ž› Ž‘ƒŽƒ–‹„‘†› ParaǦƒ‹‘–Š‹‘’Š‡‘Ž ‘Ž›‡”ƒ•‡ Šƒ‹”‡ƒ –‹‘ ‡ ‘„‹ƒ–ƒ–‹„‘†› ‡ˆ‡”‡ ‡‡Ž‡ –”‘†‡ ‹„‘— Ž‡‹ ƒ ‹† ‡ŽˆǦƒ••‡„Ž‡†‘‘Žƒ›‡”• ƒ–—”ƒ–‡† ƒŽ‘‡Ž‡Ž‡ –”‘†‡  ƒ‹‰‡Ž‡ –”‘‹ ”‘• ‘’›  ”‡‡Ǧ’”‹–‡†‡Ž‡ –”‘†‡  ”‡‡Ǧ’”‹–‡† ‡ŽŽ• —”ˆƒ ‡’Žƒ•‘”‡•‘ƒ ‡ “—ƒ”‡™ƒ˜‡˜‘Ž–ƒ‡–”› ‡–”ƒ › Ž‹‡ ”‹‹–”‘–‘Ž—‡‡ TrisȋŠ›†”‘š›‡–Š›ŽȌƒ‹‘‡–Šƒ‡ ‘”‹‰‡Ž‡ –”‘†‡ ‘”Ž†Š‡ƒ–Š‘”‰ƒ‹œƒ–‹‘ —ƒ–—†‘–• —ƒ”–œ ”›•–ƒŽ‹ ”‘„ƒŽƒ ‡.  . . ͳ͹ .

(32)  ͳͺ . AncaftefanaFlorea.  INTRODUCTION  Š‡‹ ”‡ƒ•‹‰ ‘ ‡”™‘”Ž†™‹†‡ˆ‘”‡˜‹”‘‡–’‘ŽŽ—–‹‘ǡ ‘–ƒ‹ƒ–‹‘‘ˆ ˆ‘‘†•–—ˆˆǡ†”—‰•ƒˆ‡–›ƒ†•‡ —”‹–›‹••—‡• ”‡ƒ–‡•ƒ—”‰‡ˆ‘”–Š‡†‡˜‡Ž‘’‡–‘ˆˆƒ•–ǡ •‡•‹–‹˜‡ƒ†”‡Ž‹ƒ„Ž‡‡–Š‘†•ˆ‘”–Š‡†‡–‡ –‹‘‘ˆ„‹‘Ž‘‰‹ ƒŽƒ† Š‡‹ ƒŽ ‘’‘—†•Ǥ Ž‡ –”‘ Š‡‹ ƒŽ –‡ Š‹“—‡• ƒ ’”‘˜‹†‡ ƒ ‹‡š’‡•‹˜‡ ƒ† •‡•‹–‹˜‡ –‘‘Ž ˆ‘” –Š‡†‡˜‡Ž‘’‡–‘ˆ•ƒŽŽǡ’‘”–ƒ„Ž‡†‡˜‹ ‡•–Šƒ–ƒ”‡ƒ„Ž‡–‘”ƒ’‹†Ž›†‡–‡ –•— ŠƒƒŽ›–‡• ™‹–ŠŠ‹‰Š•‡•‹–‹˜‹–›ƒ†•’‡ ‹ˆ‹ ‹–›ǤŽ‡ –”‘ Š‡‹ ƒŽ•‡•‘”•ƒ”‡‡š’‡ –‡†–‘Šƒ˜‡ƒ ‡••‡–‹ƒŽ ‹’ƒ – ‘ —Ž–‹’Ž‡ ˆ‹‡Ž†•ǡ ‹ Ž—†‹‰ ‡ƒ”Ž› †‹•‡ƒ•‡ †‹ƒ‰‘•‹• ™‹–Š „‡––‡” ‘—– ‘‡ˆ‘”’ƒ–‹‡–•ǡ†”—‰‘‹–‘”‹‰ƒ†ˆƒ•–ƒ†ƒ —”ƒ–‡†‡–‡ –‹‘‘ˆ‡˜‹”‘‡– ’‘ŽŽ—–ƒ–•ƒ†ˆ‘‘† ‘–ƒ‹ƒ–•Ǥ ‡•’‹–‡–Š‡ƒ––‡’–•–‘’”‘‰”‡••”‡•‡ƒ” Š‹–Š‡‘ ‘Ž‘‰›ˆ‹‡Ž†ǡ ƒ ‡””‡ƒ‹• ‘‡ ‘ˆ –Š‡ Ž‡ƒ†‹‰ ƒ—•‡• ‘ˆ †‡ƒ–Š ™‘”Ž†™‹†‡ǡ ƒ‹Ž› †—‡ –‘ ‹–• Žƒ–‡ †‹ƒ‰‘•‹•Ǥ Š—•ǡ –Š‡”‡ ‹• ƒ ‹ ”‡ƒ•‹‰ †‡ƒ† ˆ‘” –Š‡ †‡˜‡Ž‘’‡– ‘ˆ ”ƒ’‹† ƒ† •‡•‹–‹˜‡ †‡–‡ –‹‘ ‡–Š‘†•ˆ‘” ƒ ‡”„‹‘ƒ”‡”•–Šƒ–ƒ”‡ƒ„„‡”ƒ–Ž›‡š’”‡••‡†‹Š—ƒ•‡”—‹‡ƒ”Ž› •–ƒ‰‡• ‘ˆ ƒ ‡”Ǥ Ž‡ –”‘ Š‡‹ ƒŽ ‹—‘•‡•‘”• ƒ”‡ ƒ––”ƒ –‹˜‡ ƒ†‹†ƒ–‡• ˆ‘” –Š‡ †‡˜‡Ž‘’‡– ‘ˆ †‹ƒ‰‘•–‹  –‘‘Ž•ǡ ƒ• –Š‡› ‘„‹‡ –Š‡ •’‡ ‹ˆ‹ ‹–› ‘ˆ ƒ–‹„‘†›Ǧƒ–‹‰‡ ”‡ƒ –‹‘ ™‹–Š –Š‡ •‡•‹–‹˜‹–› ‘ˆ ‡Ž‡ –”‘ Š‡‹ ƒŽ –‡ Š‹“—‡•Ǥ ‡ ‡–Ž›ǡ ƒ’–ƒ‡”• Šƒ˜‡ „‡‡ ™‹†‡Ž› —•‡† ƒ• ƒŽ–‡”ƒ–‹˜‡• –‘ ƒ–‹„‘†‹‡•ǡ †—‡ –‘ –Š‡‹” ˜‡”•ƒ–‹Ž‡ •›–Š‡•‹• ƒ† ƒ„‹Ž‹–› –‘ †‹• ”‹‹ƒ–‡ „‡–™‡‡ •‹‹Žƒ” ‘Ž‡ —Ž‡•Ǥ ‹‰ŠŽ› •’‡ ‹ˆ‹  ƒ’–ƒ•‡•‘”• ™‡”‡ –Š—•‘„–ƒ‹‡†Ǥ ‘Ž‡ —Žƒ”Ž› ‹’”‹–‹‰ –‡ Š‹“—‡ ‹• ƒ ˜‡”•ƒ–‹Ž‡ ‡–Š‘† ˆ‘” –Š‡ •›–Š‡•‹• ‘ˆ ƒ”–‹ˆ‹ ‹ƒŽ ”‡ ‡’–‘”•ǡ ‘˜‡” ‘‹‰ •‘‡ ‘ˆ –Š‡ †”ƒ™„ƒ • ‘ˆ —•‹‰ ƒ–‹„‘†‹‡• ‘” ƒ’–ƒ‡”•Ǥ

(33) ‡š’‡•‹˜‡ ƒ–‡”‹ƒŽ• ™‹–Š •’‡ ‹ƒŽ ”‡ ‘‰‹–‹‘ ƒ„‹Ž‹–‹‡• –‘™ƒ”†• ƒ ™‹†‡ ”ƒ‰‡ ‘ˆ ‘Ž‡ —Ž‡• ƒ „‡ ‘„–ƒ‹‡†ǡ ™Š‹ Š ‡šŠ‹„‹– Š‹‰Š •–ƒ„‹Ž‹–› ‹ Šƒ”•Š ‡˜‹”‘‡–ƒŽ ‘†‹–‹‘Ǥ Š‹•”‡•‡ƒ” Š™ƒ•†‹”‡ –‡†–‘™ƒ”†•–Š‡†‡˜‡Ž‘’‡–‘ˆ˜ƒ”‹‘—•‡Ž‡ –”‘ Š‡‹ ƒŽ ƒˆˆ‹‹–› •‡•‘”• —•‹‰ †‹ˆˆ‡”‡– ”‡ ‡’–‘”• ȋƒ–‹„‘†‹‡•ǡ ƒ’–ƒ‡”• ƒ† ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡† ˆ‹Ž•Ȍ ˆ‘” –Š‡ †‡–‡ –‹‘ ‘ˆ †‹ˆˆ‡”‡– –ƒ”‰‡– ƒƒŽ›–‡• ‘ˆ ‡˜‹”‘‡–ƒŽǡ ˆ‘‘† •ƒˆ‡–›ǡ„‹‘‡†‹ ƒŽƒ†„‹‘’Šƒ”ƒ ‡—–‹ ƒŽ‹–‡”‡•–Ǥ ‡‘„Œ‡ –‹˜‡‘ˆ–Š‹•™‘”™ƒ•–‘†‡˜‡Ž‘’‡Ž‡ –”‘ Š‡‹ ƒŽ†‹ƒ‰‘•–‹ †‡˜‹ ‡•ˆ‘” ‡ƒ”Ž›†‡–‡ –‹‘‘ˆ ƒ ‡”Ǥͳ–—‘”„‹‘ƒ”‡”™ƒ• Š‘•‡ƒ•ƒ‘†‡Ž‘Ž‡ —Ž‡ƒ† ƒ–‹„‘†‹‡• ƒ† ƒ’–ƒ‡”• ™‡”‡ ‡’Ž‘›‡† ƒ• „‹‘”‡ ‘‰‹–‹‘ ‡Ž‡‡–•Ǥ ƒ‘ƒ–‡”‹ƒŽ•.

(34) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ͳͻ . ™‡”‡ ‹–‡‰”ƒ–‡† ‹ –Š‡ ’”‘’‘•‡† •‡•‘”• ƒ• ‹‘„‹Ž‹œƒ–‹‘ ’Žƒ–ˆ‘”•Ǥ ”‘–‡‹ Ǧ ƒ‰‡–‹  „‡ƒ†• ƒ† •–”‡’–ƒ˜‹†‹Ǧƒ‰‡–‹  „‡ƒ†• ™‡”‡ ‡’Ž‘›‡† ˆ‘” ƒ ƒ–‹„‘†› •ƒ†™‹ Šƒ••ƒ›ƒ†ƒƒ’–ƒ‡”•ƒ†™‹ Šƒ••ƒ›ǡ”‡•’‡ –‹˜‡Ž›Ǥ ‘Ž†ƒ‘’ƒ”–‹ Ž‡•™‡”‡ —•‡† ˆ‘” –Š‡ ‹‘„‹Ž‹œƒ–‹‘ ‘ˆ –Š‹‘Žƒ–‡† ƒ’–ƒ‡”• •’‡ ‹ˆ‹  ˆ‘” ͳ ‹ ƒ Žƒ„‡Ž ˆ”‡‡ ‘ˆ‹‰—”ƒ–‹‘Ǥ ‘–Š‡” ‘„Œ‡ –‹˜‡ ‘ˆ –Š‡ ’”‡•‡– ™‘” ™ƒ• –Š‡ †‡˜‡Ž‘’‡– ‘ˆ ‘Ž‡ —Žƒ”Ž› ‹’”‹–‡†‡Ž‡ –”‘ Š‡‹ ƒŽ•‡•‘”•ˆ‘”–Š‡†‡–‡ –‹‘‘ˆ†”—‰•ǡ‡˜‹”‘‡–’‘ŽŽ—–ƒ–• ƒ†ˆ‘‘† ‘–ƒ‹ƒ–•Ǥ‡ƒ‹‡†–‘†‡˜‡Ž‘’ƒ‰‡‡”‹ ’”‘–‘ ‘Ž–Šƒ– ‘—Ž†„‡ƒ’’Ž‹‡† –‘ ƒ „”‘ƒ† ”ƒ‰‡ ‘ˆ ‘Ž‡ —Ž‡•ǡ ‹ Ž—†‹‰ ‘Ǧ‡Ž‡ –”‘ƒ –‹˜‡ ‘’‘—†•ǡ —•‹‰ Š‡šƒ ›ƒ‘ˆ‡””‹–‡Ȁ Š‡šƒ ›ƒ‘ˆ‡””ƒ–‡ ”‡†‘š ‡†‹ƒ–‘”Ǥ

(35) ’”‹–‡† ˆ‹Ž• ™‡”‡ ’”‡’ƒ”‡† „› ‡Ž‡ –”‘’‘Ž›‡”‹œƒ–‹‘ via › Ž‹  ˜‘Ž–ƒ‡–”› ‘ˆ pǦƒ‹‘–Š‹‘’Š‡‘Ž ˆ— –‹‘ƒŽ‹œ‡† ƒ‘’ƒ”–‹ Ž‡•‹–Š‡’”‡•‡ ‡‘ˆ–‡’Žƒ–‡‘Ž‡ —Ž‡•ǤŠ‡•—„•‡“—‡–‡š–”ƒ –‹‘‘ˆ–Š‡ –‡’Žƒ–‡ ˆ”‘ –Š‡ ’‘Ž›‡” ƒ–”‹š ”‡•—Ž–• ‹ –Š‡ ˆ‘”ƒ–‹‘ ‘ˆ •’‡ ‹ˆ‹  ”‡ ‘‰‹–‹‘ ƒ˜‹–‹‡•–Šƒ–ƒ”‡ƒ„Ž‡–‘„‹†–Š‡ƒƒŽ›–‡•Ǥ ‡ƒ‹‡†ƒŽ•‘–‘‹˜‡•–‹‰ƒ–‡–Š‡’”ƒ –‹ ƒŽƒ’’Ž‹ ƒ„‹Ž‹–›‘ˆ–Š‡’”‘’‘•‡†•‡•‘”• „› ƒƒŽ›œ‹‰ ‘’Ž‡š ƒ–”‹ ‡• –Šƒ– ‘–ƒ‹ –Š‡ ƒƒŽ›–‡ǡ •— Š ƒ• –ƒ’ ƒ† ”‹˜‡” ™ƒ–‡”ǡ Š‘‡›ǡ•‡”—ƒ††”—‰ˆ‘”—Žƒ–‹‘•Ǥ . . .

(36)  ʹͲ . AncaftefanaFlorea.     STATEOFTHEART   . .

(37) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ʹͳ . 1. Generalaspectsofaffinitysensors Š‡ˆ‹‡Ž†‘ˆ•‡•‘”†‡˜‡Ž‘’‡–Šƒ•„”‘ƒ†‡‡† ‘•‹†‡”ƒ„Ž›‹”‡ ‡–›‡ƒ”•ǡ ™‹–Š ƒ ˜ƒ•– ’‘‘Ž ‘ˆ ƒ’’Ž‹ ƒ–‹‘• ‹ „ƒ•‹ ƒŽŽ› ‡˜‡”› ƒƒŽ›–‹ ƒŽ –ƒ• ˆ”‘ „‹‘‡†‹ ƒŽ ƒƒŽ›•‹• –‘ ˆ‘‘† •ƒˆ‡–› ƒ† ‡˜‹”‘‡–ƒŽ ƒƒŽ›•‹•Ǥ ‘‰ •‡•‹‰ •›•–‡•ǡ ƒˆˆ‹‹–› •‡•‘”• ”‡’”‡•‡– ƒ Žƒ”‰‡ ‰”‘—’ ‘ˆ –Š‡ Š‡‹ ƒŽ ƒ† „‹‘Ž‘‰‹ ƒŽ •‡•‘”• –Šƒ– ‰ƒ‹‡† ‹ ”‡ƒ•‡†ƒ––‡–‹‘‹–Š‡’ƒ•–ʹͲ›‡ƒ”•Ǥ ‡•‘”• ƒ”‡ †‡˜‹ ‡• –Šƒ– †‡–‡ – ƒ ’Š›•‹ ƒŽǡ Š‡‹ ƒŽ ‘” „‹‘Ž‘‰‹ ƒŽ Šƒ‰‡ ƒ† ‘˜‡”–‹–‹–‘ƒ‡ƒ•—”ƒ„Ž‡•‹‰ƒŽͳǤ  „‹‘•‡•‘” ‹• ƒ ƒƒŽ›–‹ ƒŽ †‡˜‹ ‡ –Šƒ– ‹ ‘”’‘”ƒ–‡• ƒ „‹‘Ž‘‰‹ ƒŽ ‘Ž‡ —Žƒ” ”‡ ‘‰‹–‹‘‡Ž‡‡–ƒ––Š‡•—”ˆƒ ‡‘ˆƒ–”ƒ•†— ‡”™Š‹ Š‘—–’—–•ƒ‡Ž‡ –”‹ ‘”‘’–‹ ƒŽ •‹‰ƒŽ–Šƒ–‹•†‹”‡ –Ž›”‡Žƒ–‡†–‘–Š‡ ‘ ‡–”ƒ–‹‘‘ˆ–Š‡–ƒ”‰‡–ƒƒŽ›–‡ǤŠ‡„‹‘Ž‘‰‹ ƒŽ ‘Ž‡ —Ž‡ ‘ˆ‡”• –Š‡ •‡Ž‡ –‹˜‹–› ‘ˆ –Š‡ •‡•‘”ʹǦͶǤ ƒ”‹‘—• „‹‘Ž‘‰‹ ƒŽ ‡Ž‡‡–• ƒ› „‡ ‡’Ž‘›‡† ƒ• „‹‘‡Ž‡‡–•ǡ •— Š ƒ• ‡œ›‡•ǡ ƒ–‹„‘†‹‡•ǡ ƒ’–ƒ‡”•ǡ Ȁǡ ‡ŽŽ•ǡ –‹••—‡•ǡ ˜‹–ƒ‹•ǡ ™Š‹ Š ‡ƒ„Ž‡ ”‡ ‘‰‹–‹‘ ƒ† „‹†‹‰ ‹–‡”ƒ –‹‘• ‘ˆ –Š‡ –ƒ”‰‡– ƒƒŽ›–‡™‹–ŠŠ‹‰Š•‡Ž‡ –‹˜‹–›ǤŠ‡–”ƒ•†— –‹‘‘ˆ–Š‡”‡ ‘‰‹–‹‘‡˜‡––‘ƒ‡Ž‡ –”‘‹  •‹‰ƒŽ ƒ„‡ƒ Š‹‡˜‡†„›‡Ž‡ –”‘ Š‡‹ ƒŽǡ‘’–‹ ƒŽǡ’‹‡œ‘‡Ž‡ –”‹ ƒ†–Š‡”ƒŽ‡–Š‘†•Ǥ Š‡‰‡‡”ƒŽ• Š‡‡‘ˆƒ„‹‘•‡•‘”‹•‹ŽŽ—•–”ƒ–‡†‹ ‹‰ǤͳǤ  ƒˆˆ‹‹–› •‡•‘” ƒ „‡ †‡ˆ‹‡† ƒ• ƒ ƒƒŽ›–‹ ƒŽ †‡˜‹ ‡ –Šƒ– ‹ ‘”’‘”ƒ–‡• ƒ „‹‘Ž‘‰‹ ƒŽ ”‡ ‡’–‘” ‹‘„‹Ž‹œ‡† ƒ– –Š‡ •—”ˆƒ ‡ ‘ˆ ƒ –”ƒ•†— ‡” –Šƒ– ƒ ”‡˜‡”•‹„Ž› †‡–‡ – ƒ ”‡ ‡’–‘”ǦŽ‹‰ƒ† ‹–‡”ƒ –‹‘ ™‹–Š Š‹‰Š •‡Ž‡ –‹˜‹–› ƒ† ‹ ƒ ‘Ǧ†‡•–”— –‹˜‡ ™ƒ›͵Ǥ ˆˆ‹‹–› •‡•‘”• ƒ”‡ „ƒ•‡† ‘ ‘Ž‡ —Žƒ” ”‡ ‘‰‹–‹‘ ƒ† •‡Ž‡ –‹˜‡ „‹†‹‰ ‘ˆ „‹‘‘Ž‡ —Ž‡• ȋƒ–‹„‘†‹‡•ǡ — Ž‡‹  ƒ ‹†•ǡ ”‡ ‡’–‘”•Ȍ ™‹–Š –Š‡ ƒƒŽ›–‡ ‘ˆ ‹–‡”‡•–ǡ ‡˜‡– –Šƒ– ‹• †‡–‡”‹‡† „› ‘’Ž‡‡–ƒ”‹–› ‹ •‹œ‡ ƒ† •Šƒ’‡ ‘ˆ –Š‡ „‹†‹‰ •‹–‡ –‘ –Š‡ ƒƒŽ›–‡‘ˆ‹–‡”‡•–ͷǤ—‡–‘–Š‡Š‹‰Šƒˆˆ‹‹–›ƒ†•’‡ ‹ˆ‹ ‹–›‘ˆ–Š‹•‹–‡”ƒ –‹‘ǡƒˆˆ‹‹–› •‡•‘”•‡šŠ‹„‹–Š‹‰Š•‡•‹–‹˜‹–›ƒ†•‡Ž‡ –‹˜‹–›Ǥ .  Fig.1. Š‡ƒ–‹ ”‡’”‡•‡–ƒ–‹‘‘ˆƒ„‹‘•‡•‘”.

(38)  ʹʹ . AncaftefanaFlorea. 1.2.Generalclassification ƒ”‹‘—• Žƒ••‹ˆ‹ ƒ–‹‘•ˆ‘”•‡•‘”• ƒ„‡ˆ‘—†‹–Š‡Ž‹–‡”ƒ–—”‡ǣ x.  ‘”†‹‰–‘–Š‡–”ƒ•†— –‹‘’”‹ ‹’Ž‡•ǣ o. Opticalǣ „ƒ•‡† ‘ –Š‡ ‘˜‡”•‹‘ ‘ˆ Ž‹‰Š– ”ƒ›• ‹–‘ ‡Ž‡ –”‘‹  •‹‰ƒŽ• ȋˆŽ—‘”‡• ‡ ‡ǡƒ„•‘”„–‹‘ǡ”‡ˆŽ‡ –‹‘ȌǢ–Š‡›Šƒ˜‡–Š‡ƒ†˜ƒ–ƒ‰‡‘ˆŠ‹‰Š •‡•‹–‹˜‹–›ǡ™‹†‡†›ƒ‹ ”ƒ‰‡ƒ†—Ž–‹’Ž‡š‹‰ ƒ’ƒ„‹Ž‹–‹‡•Ǣ. o. Thermalǣ —•‡• –Š‡”ƒŽ ‡ˆˆ‡ –• –‘ ‡ƒ•—”‡ ’Š›•‹ ƒŽ ’ƒ”ƒ‡–‡”• ƒ† ‹˜‘Ž˜‡• ƒ –”ƒ•†— –‹‘ ‹ –™‘ •–‡’•ǣ ˆ‹”•– –Š‡ ‹’—– •‹‰ƒŽ ‹• –”ƒ•†— ‡† ‹ ƒ –Š‡”ƒŽ •‹‰ƒŽǡ ™Š‹ Š ‹• –Š‡ –”ƒ•†— ‡† ‹ ƒ ‡Ž‡ –”‹ ƒŽ•‹‰ƒŽǢ. o. Mass (piezoelectric)ǣ „ƒ•‡† ‘ –Š‡ ‡ƒ•—”‡‡– ‘ˆ –Š‡ ˜‹„”ƒ–‹‘ƒŽ ˆ”‡“—‡ › ‘ˆ –Š‡ “—ƒ”–œ ”›•–ƒŽǡ ™Š‹ Š ‹ ƒ‹” †‡’‡†• ‘ –Š‡ ƒ•• ‘ˆ –Š‡ ”›•–ƒŽƒ†–Š‡‹‘„‹Ž‹œ‡†ƒƒŽ›–‡͸Ǥ. o. Electrochemicalǣƒ”‡–Š‡‘•–™‹†‡Ž›—•‡†ƒ† ƒ„‡ ƒ–‡‰‘”‹œ‡†‹ǣ ƒ. PotentiometricȂ„ƒ•‡†‘†‡–‡”‹ƒ–‹‘‘ˆ–Š‡’‘–‡–‹ƒŽ†‹ˆˆ‡”‡ ‡ „‡–™‡‡ –™‘ ‡Ž‡ –”‘†‡• Ǧ ‘‡ ”‡ˆ‡”‡ ‡ ‡Ž‡ –”‘†‡ ƒ† ‘‡ •‡•‹–‹˜‡ ‡Ž‡ –”‘†‡ ™Š‹ Š ƒ „‡ •’‡ ‹ˆ‹  ȋ‡Ǥ‰ ’  ‡Ž‡ –”‘†‡•ǡ ‹‘‹  ‡Ž‡ –”‘†‡•ȌǢ –Š‡› Šƒ˜‡ ƒ ™‹†‡” ”ƒ‰‡ ‘ˆ †‡–‡ –‹‘ǡ „—– Ž‘™‡” •‡•‹–‹˜‹–›ǡ–Šƒ‘–Š‡”‡Ž‡ –”‘ Š‡‹ ƒŽ–‡ Š‹“—‡•Ǣ. ƒ. Conductimetric Ǧ „ƒ•‡† ‘ ƒŽ–‡”‹‰ –Š‡ ‘†— –‹˜‹–› ‘ˆ –Š‡ •ƒ’Ž‡ •‘Ž—–‹‘Ǣ –Š‡› Šƒ˜‡ –Š‡ †”ƒ™„ƒ • ‘ˆ Ž‘™ •‡Ž‡ –‹˜‹–› ƒ† ‹–‡”ˆ‡”‡ ‡‹”‡ƒŽ•ƒ’Ž‡•Ǣ. ƒ. Amperometric Ȃ „ƒ•‡† —’‘ –Š‡ ‡ƒ•—”‡‡– ‘ˆ –Š‡ —””‡– ‰‡‡”ƒ–‡†„›–Š‡‘š‹†ƒ–‹‘‘””‡†— –‹‘‘ˆ‡Ž‡ –”‘ƒ –‹˜‡•’‡ ‹‡•ƒ– ƒ ‘•–ƒ–’‘–‡–‹ƒŽǤ. x.  ‘”†‹‰ –‘ –Š‡ ‹–‡”ƒ –‹‘ ‘†‡ „‡–™‡‡ –Š‡ ‡†‹— ƒ† –Š‡ •‡•‘” ȋ•—”ˆƒ ‡‘”˜‘Ž—‡‹–‡”ƒ –‹‘Ȍʹ. x.  ‘”†‹‰–‘–Š‡ƒ–—”‡‘ˆ–Š‡„‹‘Ž‘‰‹ ƒŽ”‡ ‘‰‹–‹‘’”‘ ‡••ǣ o. Biocatalytic sensorsǣ ‹ ‘”’‘”ƒ–‡ ‡œ›‡•ǡ ‹ ”‘‘”‰ƒ‹••ǡ ‡ŽŽ•ǡ –‹••—‡• ƒ† „‹‘‹‡–‹  ƒ–ƒŽ›•–• –‘ ”‡ ‘‰‹œ‡ –Š‡ ƒƒŽ›–‡ ‘ˆ ‹–‡”‡•– ƒ†’”‘†— ‡‡Ž‡ –”‘ƒ –‹˜‡•’‡ ‹‡•‘”‘–Š‡”†‡–‡ –ƒ„Ž‡‘—– ‘‡Ǥ. o. Affinitysensorsǣ„ƒ•‡†‘ƒ•‡Ž‡ –‹˜‡„‹†‹‰‹–‡”ƒ –‹‘„‡–™‡‡–Š‡ ƒƒŽ›–‡ ƒ† ƒ „‹‘‡Ž‡‡– •— Š ƒ• ƒ–‹„‘†›ǡ — Ž‡‹  ƒ ‹†ǡ ”‡ ‡’–‘” ’”‘–‡‹•‘”•›–Š‡–‹ ”‡ ‡’–‘”•ͷǡ͸Ǥ.

(39) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ʹ͵ . x  ‘”†‹‰ –‘ ‹–• —•‡ǣ ‘–”‘Ž ‘ˆ ƒ‹” ƒ† ™ƒ–‡” ’‘ŽŽ—–‹‘ǡ Š‡ƒŽ–Šǡ †‡ˆ‡•‡ ƒ† •‡ —”‹–›ǡˆ‘‘†ƒ†’”‘ ‡•• ‘–”‘Žǡ„‹‘‡†‹ ƒŽˆ‹‡Ž†‡– ʹǤ. 1.3.Voltamperometricsensors Ž‡ –”‘ Š‡‹ ƒŽ„‹‘•‡•‘”• —””‡–Ž›†‘‹ƒ–‡–Š‡•‡•‹‰†‡˜‹ ‡•ˆ‹‡Ž†ǡ†—‡ –‘ –Š‡‹” •‹’Ž‹ ‹–›ǡ Ž‘™ ‘•– ƒ† Š‹‰Š •‡•‹–‹˜‹–›Ǥ Š‡ ‰”‘™–Š ‹ –Š‡ ˆ‹‡Ž† ‘ˆ ‡Ž‡ –”‘ Š‡‹ ƒŽ „‹‘•‡•‘”• Šƒ• „‡‡ ”‡ƒ”ƒ„Ž‡ •‹ ‡ –Š‡ †‡˜‡Ž‘’‡– ‘ˆ –Š‡ ˆ‹”•– „‹‘•‡•‘”„›Žƒ”‹ͳͻ͸ʹ͹Ǥ Š‡”‡ƒ”‡ƒ‹Ž›–Š”‡‡ ƒ–‡‰‘”‹‡•‘ˆ‡ƒ•—”‡‡–ˆ‘”‡Ž‡ –”‘ Š‡‹ ƒŽ‡–Š‘†•ǣ —””‡–ǡ ’‘–‡–‹ƒŽ ƒ† ‹’‡†ƒ ‡Ǥ Š‡ ‘•– ‘‘Ž› —•‡† –‡ Š‹“—‡ ‹ •‡•‘”•ǯ †‡˜‡Ž‘’‡– ‹• –Š‡ ˆ‘”‡” Žƒ••Ǥ

(40)  ˜‘Ž–ƒ‡–”‹  ƒ† ƒ’‡”‘‡–”‹  ‡–Š‘†• ƒ ’‘–‡–‹ƒŽ ‹• ƒ’’Ž‹‡† ƒ† –Š‡ —””‡– ”‡•—Ž–‡† „› –Š‡ ‡Ž‡ –”‘ Š‡‹ ƒŽ ‘š‹†ƒ–‹‘ ‘” ”‡†— –‹‘‹•‡ƒ•—”‡†Ǥ

(41) ˜‘Ž–ƒ‡–”‹ –‡ Š‹“—‡•–Š‡’‘–‡–‹ƒŽ‹•• ƒ‡†‘˜‡”ƒ•‡– ‘ˆ ’‘–‡–‹ƒŽ ”ƒ‰‡ǡ ™Š‹Ž‡ ‹ ƒ’‡”‘‡–”› –Š‡ ’‘–‡–‹ƒŽ ‹• ƒ‹–ƒ‹‡† ‘•–ƒ–Ǥ ’‡”‘‡–”‹  †‡–‡ –‹‘ ‹• ‘‘Ž› —•‡† ™‹–Š „‹‘ ƒ–ƒŽ›–‹  ƒ† ƒˆˆ‹‹–› •‡•‘”• „‡ ƒ—•‡‘ˆ‹–••‹’Ž‹ ‹–›ƒ†Ž‘™†‡–‡ –‹‘Ž‹‹–ͷǤ ‡’‡†‹‰ ‘ –Š‡ ƒƒŽ›–‹  ’”‹ ‹’Ž‡ ‹˜‘Ž˜‡†ǡ ƒ’‡”‘‡–”‹  •‡•‘”• ƒ „‡ Žƒ••‹ˆ‹‡†‹–Š”‡‡ƒ‹ ƒ–‡‰‘”‹‡•ǣ x. Analysis by preǦconcentrationǡ ”‡“—‹”‡• –Š‡ ’”‡•‡ ‡ ƒ– –Š‡ •—”ˆƒ ‡ ‘ˆ –Š‡ ‡Ž‡ –”‘†‡ ‘ˆ ƒ ‘’Ž‡š‹‰ ƒ‰‡– ‘” ‘Ž‡ —Žƒ” ”‡ ‘‰‹–‹‘ ‡Ž‡‡–• –Šƒ– •‡Ž‡ –‹˜‡Ž› ’”‡ ‘ ‡–”ƒ–‡ ƒ ‰‹˜‡ ƒƒŽ›–‡Ǥ Š‹• Ž‡ƒ†• –‘ –Š‡ ‹ ”‡ƒ•‡ ‘ˆ –Š‡ Ž‘ ƒŽ ‘ ‡–”ƒ–‹‘ ‘ˆ –Š‡ ƒƒŽ›–‡ ƒ– –Š‡ –Š‡ ‡Ž‡ –”‘†‡ •—”ˆƒ ‡ǡ ’”‹‘” –‘ †‡–‡ –‹‘‹–•‡Žˆǡ‹‘”†‡”–‘’‡”ˆ‘”–Š‡†‡–‡ –‹‘‹˜‡”›†‹Ž—–‡†‡†‹ƒǤ. x. Direct electrocatalytic detectionǡ ™Š‹ Š —•‡• ‡Ž‡ –”‘ –”ƒ•ˆ‡” ƒ ‡Ž‡”ƒ–‹‰ ƒ‰‡–• ȋ Š‡‹ ƒŽ ‡†‹ƒ–‘”• ‘” ‡Ž‡ –”‘†‡ ƒ–‡”‹ƒŽ ƒ –‹‰ ƒ• •‘Ž‹† •–ƒ–‡ ƒ–ƒŽ›œ‡”Ȍǡ–Šƒ–‹ ”‡ƒ•‡•–Š‡•‡•‹–‹˜‹–›‘ˆ†‡–‡ –‹‘Ǥ. x. Indirect amperometric detectionǡ ˆ‘” •’‡ ‹‡• –Šƒ– ƒ”‡ ‘– ‡Ž‡ –”‘ƒ –‹˜‡ǡ „—– ™Š‹ Š’‡”–—”„–Š‡‡Ž‡ –”‘ Š‡‹ ƒŽ’”‘’”‹‡–‹‡•‘ˆƒ‡Ž‡ –”‘†‡ʹǤ. ‡”Šƒ’• –Š‡ ‘•– ‹’‘”–ƒ– ƒ†˜ƒ–ƒ‰‡ ‘ˆ ‡Ž‡ –”‘ Š‡‹ ƒŽ „‹‘•‡•‘”• ‹• –Šƒ– –Š‡›‡•—”‡‹‘‡†‡˜‹ ‡„‘–Š–Š‡•‡•‹–‹˜‹–›–‘™ƒ”†•–Š‡‡ƒ•—”‡†“—ƒ–‹–›ƒ†–Š‡ –”ƒ•†— –‹‘ ‹–‘ ƒ ‡Ž‡ –”‹  •‹‰ƒŽǡ ™Š‹ Š ‹• ‡ƒ•‹Ž› ƒ† †‹”‡ –Ž› ƒ†ƒ’–ƒ„Ž‡ǡ ‹ ‘•– ƒ•‡•ǡ –‘ ƒ ‡ƒ•—”‹‰ ‹•–”—‡–ʹǤ Ž‡ –”‘ Š‡‹ ƒŽ „‹‘•‡•‘”• Šƒ˜‡ –Š‡ ƒ†˜ƒ–ƒ‰‡ ‘ˆ Š‹‰Š •’‡ ‹ˆ‹ ‹–› †—‡ –‘ –Š‡ ‹ ‘”’‘”ƒ–‡† „‹‘‡Ž‡‡–ǡ •Š‘”– ”‡•’‘•‡ –‹‡ ȋ‹ ‰‡‡”ƒŽ •Š‘”–‡”–Šƒͳ‹ȌǡŽ‘™ ‘•–ǡ‡ƒ•‡‘ˆ—•‡ǡƒ•™‡ŽŽƒ•–Š‡’‘••‹„‹Ž‹–›‘ˆ‹‹ƒ–—”‹œƒ–‹‘ ƒ† ƒ—–‘ƒ–‹‘Ǥ ‘”‡‘˜‡” –Š‡› ‰‹˜‡ ”ƒ’‹† ƒ† •’‡ ‹ˆ‹  †‡–‡ –‹‘ ‘ˆ ƒƒŽ›–‡• ‹ ‘’Ž‡š ‡†‹ƒ •— Š ƒ• „Ž‘‘†ǡ ’Žƒ•ƒǡ —”‹‡ǡ ”‹˜‡” ™ƒ–‡”•ǡ ˆ‘‘† ƒ–”‹ ‡• ‡– ǡ ‡Ž‹‹ƒ–‹‰ –Š‡ ‡‡† ˆ‘” •ƒ’Ž‡ ’”‡’ƒ”ƒ–‹‘ ™Š‹ Š ƒ‡• –Š‡ •—‹–ƒ„Ž‡ ˆ‘”.

(42)  ʹͶ . AncaftefanaFlorea. ƒ’’Ž‹ ƒ–‹‘ ‹ ƒ ™‹†‡ ”ƒ‰‡ ‘ˆ ˆ‹‡Ž†•Ǥ Š‡ „‹‰‰‡•– ’‘”–‹‘ ‘ˆ –Š‡ †‡˜‡Ž‘’‡† ‡Ž‡ –”‘ Š‡‹ ƒŽ •‡•‘”• ‹• ˆ‘” Š‡ƒŽ–Š ƒ”‡ ƒ† †‹•‡ƒ•‡ †‹ƒ‰‘•‹•Ǣ ‘–Š‡” ˆ‹‡Ž†• ‹ Ž—†‡ ˆ‘‘† ‹†—•–”›ǡ ’Šƒ”ƒ ‡—–‹ ƒŽ ƒƒŽ›•‹•ǡ •’‘”–ǡ ƒ–‹‘ƒŽ †‡ˆ‡•‡ ƒ† †‘‡•–‹  •ƒˆ‡–›ǡ ‡˜‹”‘‡–ƒŽƒƒŽ›•‹•ʹǡ͵ǡͷǤ‘‡‘ˆ–Š‡†”ƒ™„ƒ •‹ Ž—†‡–Š‡’”‘„Ž‡ƒ–‹ •–ƒ„‹Ž‹–›‘ˆ –Š‡„‹‘‡Ž‡‡–ǡ™Š‹ Š‹••‡•‹–‹˜‡ƒ† ƒ„‡ƒŽ–‡”‡†—†‡”‡˜‹”‘‡–ƒŽ ‘†‹–‹‘• •— Šƒ•’ ‘”–‡’‡”ƒ–—”‡ǡƒ•™‡ŽŽƒ•–Š‡Š‡–‡”‘‰‡‡‹–›‘ˆ–Š‡‹‘„‹Ž‹œ‡†”‡ ‡’–‘”ƒ– –Š‡•—”ˆƒ ‡‘ˆ–Š‡–”ƒ•†— ‡”•Ǥ. 1.4.Impedimetricsensors Ž‡ –”‘ Š‡‹ ƒŽ ‹’‡†ƒ ‡ •’‡ –”‘• ‘’› ȋ

(43) Ȍ ‹• ƒ ‡ˆˆ‡ –‹˜‡ ƒ† •‡•‹–‹˜‡ •—”ˆƒ ‡ Šƒ”ƒ –‡”‹œƒ–‹‘ –‡ Š‹“—‡ ™‹†‡Ž› —•‡† ‹ Š‡‹ ƒŽ •‡•‘”• ƒ† „‹‘•‡•‘”• Šƒ˜‹‰–Š‡ƒ‹ƒ†˜ƒ‰‡‘ˆŽƒ„‡ŽǦˆ”‡‡†‡–‡ –‹‘ͺǤ

(44) – ƒ„‡‡’Ž‘›‡†ˆ‘”–Š‡†‡–‡ –‹‘ ‘ˆƒƒŽ›–‡•‹Ž‘™ ‘ ‡–”ƒ–‹‘•ͻƒ†ˆ‘”–Š‡•–—†›‘ˆ‡Ž‡ –”‘†‡Ȁ‡Ž‡ –”‘Ž›–‡‹–‡”ˆƒ ‡ ƒ† ‡Ž‡ –”‘†‡ •—”ˆƒ ‡ ‹‡–‹ •ͳͲǤ 

(45)  ‹• „ƒ•‡† ‘ –Š‡ ‡ƒ•—”‡‡– ‘ˆ ”‡•‹•–‹˜‡ ƒ† ƒ’ƒ ‹–‹˜‡’”‘’‡”–‹‡•‘ˆƒ–‡”‹ƒŽ•Ǥ’‘–‡–‹ƒŽ‹•ƒ’’Ž‹‡†–‘ƒ‡Ž‡ –”‘ Š‡‹ ƒŽ ‡ŽŽ ƒ† –Š‡ ”‡•—Ž–‡†  —””‡– •‹‰ƒŽ ‹• ‡ƒ•—”‡†Ǥ Š‡ ˆ—†ƒ‡–ƒŽ ‘ˆ ƒ •’‡ –”— ‹• ˆ”‡“—‡ ›ǣƒ‹’‡†ƒ ‡•’‡ –”—‹•‘„–ƒ‹‡†„›˜ƒ”›‹‰–Š‡ˆ”‡“—‡ ›‘˜‡”ƒ™‹†‡ ”ƒ‰‡ͷǤ  ‘”†‹‰ –‘ Šǯ• Žƒ™ǡ ”‡•‹•–ƒ ‡ ƒ „‡ †‡ˆ‹‡† ƒ• –Š‡ ”ƒ–‹‘ „‡–™‡‡ ’‘–‡–‹ƒŽǡǡƒ† —””‡–ǡ

(46) Ǣ–Š—•–Š‡‹’‡†ƒ ‡‘ˆƒ•›•–‡ ƒ„‡ ƒŽ —Žƒ–‡†—•‹‰–Š‡ ˆ‘ŽŽ‘™‹‰‡“—ƒ–‹‘ǣ  ܼൌ. ‫‹• Ͳܧ‬ሺ߱‫ݐ‬ሻ •‹ሺ߱‫ݐ‬ሻ ‫ܧ‬௧ ൌ ൌ ܼͲ  ‫ܫ‬௧ ‫‹• Ͳܫ‬ሺ߱‫ ݐ‬൅ ߔሻ •‹ሺ߱‫ ݐ‬൅ ߔሻ.  Š‡”‡‹•‹’‡†ƒ ‡ǡ–’‘–‡–‹ƒŽƒ––‹‡–ǡ

(47) – —””‡–ƒ––‹‡–ǡͲƒ†

(48) Ͳ•‹‰ƒŽ ƒ’Ž‹–—†‡•ǡ ɘ ˆ”‡“—‡ › ƒ† ߔ ’Šƒ•‡ •Š‹ˆ– „‡–™‡‡ – ƒ†

(49) –ͷǤ

(50) ’‡†ƒ ‡ ‹• –Š—• ‡š’”‡••‡†‹–‡”•‘ˆƒ‰‹–—†‡Ͳƒ†’Šƒ•‡•Š‹ˆ–ߔǤ 

(51)  ƒ„‡’‡”ˆ‘”‡†‹–™‘™ƒ›•ǣ x. faradaic impedance Ȃ ™Š‡ ‡Ž‡ –”‘ Š‡‹ ƒŽ ”‡†‘š ”‡ƒ –‹‘• ‘ —” –Šƒ– ‰‡‡”ƒ–‡‡Ž‡ –”‘•ǡ™Š‹ Šƒ”‡–”ƒ•ˆ‡””‡†–Š”‘—‰Š–Š‡‡Ž‡ –”‘†‡•—”ˆƒ ‡Ǣ–Š‡•‡ ‡Ž‡ –”‘• ‘ˆ”‘– ƒ ”‡•‹•–ƒ ‡ ƒ‰ƒ‹•– –Š‡‹” –”ƒ•ˆ‡” –‘™ƒ”†• –Š‡ •—”ˆƒ ‡ ‘ˆ –Š‡‡Ž‡ –”‘†‡ǡ™Š‹ Š‹• ƒŽŽ‡†ˆƒ”ƒ†ƒ‹ ‹’‡†ƒ ‡Ǥ. x. nonǦfaradaicimpedanceȂ‹•ƒˆ‘”‘ˆ‹’‡†ƒ ‡ǡ‹–•‡Ž‡ –”‹ ƒŽ’”‘’‡”–‹‡• „‡‹‰‰‡‡”ƒ–‡†„›†‘—„Ž‡Žƒ›‡” ƒ’ƒ ‹–ƒ ‡ͺǤ. Š‡†‹ƒ‰”ƒ‘ˆ–Š‡

(52) ‡ƒ•—”‡‡–‹•”‡’”‡•‡–‡†„›–Š‡›“—‹•–’Ž‘–™Š‹ Š ‹ Ž—†‡•–Š‡‹ƒ‰‹ƒ”›’ƒ”–‘ˆ‹’‡†ƒ ‡ǡǦǡ‘ƒš‹•ƒ†–Š‡”‡ƒŽ’ƒ”–ǡǡ‘ƒš‹•Ǥ.

(53) . Ž‡ –”‘ Š‡‹ ƒŽƒˆˆ‹‹–›•‡•‘”•ˆ‘”„‹‘‡†‹ ƒŽǡ‡˜‹”‘‡–ƒŽƒ†ˆ‘‘†•ƒˆ‡–›ƒ’’Ž‹ ƒ–‹‘•. ʹͷ . ‘”’”‘’‡”†ƒ–ƒ ƒŽ —Žƒ–‹‘ƒ‹’‡†‹‡–”‹ ‘†‡Ž ‹” —‹–—•–„‡†‡•‹‰‡†ȋƒ†Ž‡•• ‡ŽŽ ‹” —‹–Ȍǡ ™Š‹ Š ‹ Ž—†‡ ƒ• ‡Ž‡‡–• ‡Ž‡ –”‘Ž›–‡ •‘Ž—–‹‘ ”‡•‹•–ƒ ‡ ȋ•Ȍǡ ‡Ž‡ –”‘ –”ƒ•ˆ‡” ”‡•‹•–ƒ ‡ ȋ‡–Ȍǡ ƒ”„—”‰ ‹’‡†ƒ ‡ǡ ȋȌ ƒ† ƒ’ƒ ‹–ƒ ‡ ȋȌǤ Š—•ǡ –Š‹• ‹” —‹–‘†‡Ž”‡’”‡•‡–•–Š‡‡Ž‡ –”‘–”ƒ•ˆ‡”ƒ„‹Ž‹–›‘ˆ–Š‡Žƒ›‡”‘‡Ž‡ –”‘†‡•—”ˆƒ ‡ ȋ‡–Ȍǡ ƒ•• –”ƒ•ˆ‡” ȋȌ ƒ† ‡Ž‡ –”‘†‡ •—”ˆƒ ‡ ƒ’ƒ ‹–ƒ ‡ ȋ†ŽȌͺǤ 

(54)  ‹• ™‹†‡Ž› —•‡† ˆ‘” –Š‡ ‘•–”— –‹‘ ‘ˆ Žƒ„‡ŽǦˆ”‡‡ ƒˆˆ‹‹–› •‡•‘”•ǡ ™‹–Š –Š‡ ƒ†˜ƒ–ƒ‰‡• ‘ˆ ‡ƒ•‡ ‘ˆ †‡–‡ –‹‘ǡ Ž‘™ ‘•–ǡ ‘ •ƒ’Ž‡ ’”‡–”‡ƒ–‡–ǡ ‹•‡•‹–‹˜‹–› –‘ ‘•– ‡˜‹”‘‡–ƒŽ †‹•–—”„ƒ ‡•ƒ†–Š‡•—‹–ƒ„‹Ž‹–›ˆ‘”–Š‡†‡–‡ –‹‘‘ˆƒ›–›’‡•‘ˆ‘Ž‡ —Ž‡•–Šƒ–‡šŠ‹„‹– ‹–‡”ƒ –‹‘• „‡–™‡‡ ƒ ”‡ ‘‰‹–‹‘ ”‡ ‡’–‘” ƒ† ƒƒŽ›–‡ͷǡͺǤ Š‡ ‡–Š‘† „‡ ƒ‡ ’ƒ”–‹ —Žƒ”Ž› ƒ––”ƒ –‹˜‡ ‹ –Š‡ ‹—‘•‡•‘”• ˆ‹‡Ž†ǡ ™Š‡”‡ –Š‡ ˆ‘”ƒ–‹‘ ‘ˆ ƒ–‹„‘†›Ǧ ƒ–‹‰‡ ƒ „‡ †‹”‡ –Ž› ‘‹–‘”‡† ™‹–Š‘—– –Š‡ ‡‡† ‘ˆ ˆ—”–Š‡” Žƒ„‡Ž‹‰ǡ „› •‹’Ž› ‘‹–‘”‹‰–Š‡ Šƒ‰‡‹–Š‡‡Ž‡ –”‘–”ƒ•ˆ‡””‡•‹–ƒ ‡™Š‡–Š‡ƒƒŽ›–‡„‹†•Ǥ‘‡ Ž‹‹–ƒ–‹‘•‘ˆ–Š‡‡–Š‘†‹ Ž—†‡–Š‡†‹ˆˆ‹ —Ž–›‹•—”ˆƒ ‡”‡‰‡‡”ƒ–‹‘ǡ‡•’‡ ‹ƒŽŽ›ˆ‘” ƒ–‹„‘†‹‡•™‹–ŠŠ‹‰Šƒˆˆ‹‹–› ‘•–ƒ–•ǡƒ†‹‹‹‹œ‹‰‘•’‡ ‹ˆ‹ ƒ†•‘”’–‹‘ͷǤ. 1.5.. Singleusesensors.  ”‡‡ ’”‹–‡† ‡Ž‡ –”‘†‡• ȋ•Ȍ ƒ”‡ †‹•’‘•ƒ„Ž‡ ‹‹‡Ž‡ –”‘†‡• ’ƒ––‡”‡† ™‹–Š ™‘”‹‰ǡ ”‡ˆ‡”‡ ‡ ƒ† ‘—–‡” ‡Ž‡ –”‘†‡• ȋ ‹‰Ǥ ʹȌ ƒ† Šƒ˜‡ ‰ƒ‹‡† ‹ ”‡ƒ•‡† ’‘’—Žƒ”‹–› ‹ ‡Ž‡ –”‘ Š‡‹ ƒŽ „‹‘•‡•‘”• †—‡ –‘ –Š‡‹” Ž‘™ ‘•– ƒ† ‡ƒ•‡ ‘ˆ ƒ•• ’”‘†— –‹‘—•‹‰–Š‹ ˆ‹Ž–‡ Š‘Ž‘‰›ͳͳǤŠ‡›ƒ”‡ˆƒ„”‹ ƒ–‡†—•‹‰–Š‡• ”‡‡’”‹–‹‰ –‡ Š‹“—‡ ™Š‹ Š ‹˜‘Ž˜‡• ƒ •‡“—‡–‹ƒŽ †‡’‘•‹–‹‘ ‘ˆ –Š‹  ˆ‹Ž• ‘ ƒ •‘Ž‹† •—„•–”ƒ–‡ ™Š‹ Š ’‡”‹–• –‘ ‘„–ƒ‹ ƒŽŽǦ•‘Ž‹†Ǧ•–ƒ–‡ǡ ˆŽƒ– ƒ† ‡ Šƒ‹ ƒŽŽ› ”‘„—•– •‡•‘”•Ǥ Š‡ ‡–Š‘†• ‘•‹•– ‹ –Š‡ †‡’‘•‹–‹‘ ‘ˆ ƒ ‰”ƒ’Š‹–‹  ‹ –‘ –Š‡ •‘Ž‹† •—„•–”ƒ–‡ –Š”‘—‰Š ƒ ƒ• ‘˜‡”‹‰ ‹–• •—”ˆƒ ‡Ǣ †‹ˆˆ‡”‡– ‹• ƒ† ƒ•• ƒ „‡ —•‡† –‘ ‘„–ƒ‹ ˜ƒ”‹‘—• ’ƒ––‡”•ƒ† ‘ˆ‹‰—”ƒ–‹‘•Ǥ–Š‡”ƒŽ–”‡ƒ–‡–‹•–Š‡ƒ’’Ž‹‡†–‘”‡‘˜‡–Š‡•‘Ž˜‡– ƒ† ƒ ‹•—Žƒ–‹‰ Žƒ›‡” ƒ ƒŽ•‘ „‡ ƒ’’Ž‹‡† ‹ ‘”†‡” –‘ †‡Ž‹‹–ƒ–‡ –Š‡ •—”ˆƒ ‡ ‘ˆ –Š‡ ‡Ž‡ –”‘†‡• ƒ‹–ƒ‹‹‰ ‡Ž‡ –”‹ ƒŽ ‘–ƒ –• ‘ –Š‡ ‘‡ •‹†‡ʹǤ Š‡ ƒ‹ ƒ†˜ƒ–ƒ‰‡• ‘ˆ –Š‡•‡‹†‘ˆ‡Ž‡ –”‘†‡•‹ Ž—†‡ǣ–Š‡‡Ž‹‹ƒ–‹‘‘ˆ•—”ˆƒ ‡ˆ‘—Ž‹‰ǡƒ•–Š‡› ƒ„‡—•‡† ‘‡ –‹‡ ƒ† ”‡’Žƒ ‡† ™‹–Š ‘–Š‡” ‡Ž‡ –”‘†‡• ˆ”‘ –Š‡ •ƒ‡ „ƒ– ŠǢ ‘–ƒ‹ƒ–‹‘ ‹• ƒ˜‘‹†‡†™Š‡—•‡†ˆ‘”–Š‡ƒƒŽ›•‹•‘ˆ„‹‘Ž‘‰‹ ƒŽŽ‹“—‹†•„‡‹‰†‹• ƒ”†‡†ƒˆ–‡”‘‡—•‡Ǣ –Š‡›ƒ”‡•—‹–ƒ„Ž‡ˆ‘”—•‡‹ˆŽ‘™ƒƒŽ›•‹•ƒ†ˆ‘”’‘”–ƒ„Ž‡†‡˜‹ ‡ˆ‘”insitu‘‹–‘”‹‰Ǣ —•‡‘ˆŽ‘™˜‘Ž—‡•‘ˆ•ƒ’Ž‡•†—‡–‘–Š‡‹”•ƒŽŽ†‹‡•‹‘•ͳʹǤŽ‹‹–ƒ–‹‘‘ˆ‹• –Š‡—•‡‘ˆ‘”‰ƒ‹ •‘Ž˜‡–•™Š‹ Š‹‰Š–Ž‡ƒ†–‘–Š‡†‹••‘Ž—–‹‘‘ˆ–Š‡‹Ǥ.

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La personne recrutée s’intégrera dans l’équipe pédagogique responsable des enseignements du département GEII (Génie Electrique et Informatique Industrielle) de l’IUT Lyon 1..

N ordre Année THESE DE L UNIVERSITE DE LYON Délivrée par L UNIVERSITE CLAUDE BERNARD LYON1

La protéine intégrase étant nécessaire pour d’autres processus du cycle viral, tels que la réverse transcription et/ou l’assemblage des virions, les mutants du core de la

UNIVERSITE CLAUDE BERNARD

Proposer des valeurs pour Vhmin la tension minimale associee a un niveau haut I Vbmax la tension maximale associee a un niveau bas.. Etablir la table de verite

UNIVERSITE CLAUDE BERNARD

Au fil de notre réflexion clinique, nous avons établi qu’habiter un logement nécessitait certains prérequis, comme pouvoir habiter son corps, sa subjectivité, son

UNIVERSITE CLAUDE BERNARD - LYON I DEPARTEMENT DE BIOLOGIE HUMAINE

Car même si certains auteurs parlent de surévaluation des troubles psychopathologiques, que ce soit une surévaluation dans leur définition (certains troubles régressent