Abstract Electrochemical sensors are simple, fast, accurate, and low-cost analytical devices. They are especially important to the field of healthcare since they enable measurement of important indicators of patient health such as electrolytes and glucose in blood. Continued development and improvements in electrochemical sensors can result in more accessible, affordable, and effective diagnoses and treatment strategies. Electrochemical sensors employ electrodes, usually modified with a recognition agent specific for the analyte (the biomolecule of interest). The presence of the analyte at the electrode surface is typically measured through an electrochemical reaction that generates a signal in the form of an electric current or difference in electric potential. As an alternative, electrochemiluminescence, a phenomenon whereby an electrochemical reaction generates a product in an electronically excited state that is capable of emitting light, has great benefits due to its high sensitivity, selectivity, and extremely low background signal. Here we employ a camera equipped with a complementary metal-oxide semiconductor (CMOS) detector that is interfaced with a simple zoom lens to measure ECL generated at low-cost pencil graphite electrodes and small electrode arrays using tris(2,2′- bipyridyl) dichlororuthenium(II) hexahydrate ([Ru(bpy)3]2+) with tri-n-propylamine (TPA) as the coreactant. ECL signals produced at pencil graphite working electrodes were linear with respect to [Ru(bpy)3]2+ concentrations for 45–450μM [Ru(bpy)3]2+. The detection limit was found to be 2µM using the CMOS camera with exposure time set at 10s. This proof-of-concept work suggests the pencil graphite electrode with simple imaging system platform can be applied for ECL-based biosensing strategies.

In an electrochemical sensor, the sensing performance is mainly dependent on the mass transport of the analyte towards the working electrode-electrolyte interface and working electrode properties. Carbon nanomaterials like carbon nanotubes are widely employed to modify the working electrode properties for sensitive detection. A simulation model is formulated to investigate the effects of modifying a planar bare electrode with carbon nanotubes on electrochemical detection of fenitrothion (FT, an organophosphate). The model revealed that porous electrodes caused the change in mass transport regime and influenced FT’s electrochemical response. The results aided in understanding the influence of the porous electrode on analyte detection and thus assisted in the fabrication of an ultrasensitive electrochemical sensor. Simulation supported synthesis of a highly sensitive ink to produce highly porous and electrocatalytic electrodes. Activated carbon (AC) possesses high porosity and surface area, but they suffer from lower electrical conductivity. To enhance their conductivity, AC was co-doped with nitrogen and sulfur. Multiwalled carbon nanotubes were incorporated to further improve their porosity and electrocatalytic properties. The synthesized nitrogen-sulfur co-doped activated carbon coated multiwalled carbon nanotube (NS-AC-MWCNT) ink produced highly porous electrocatalytic electrodes. The sensor revealed a 4.9 nM limit of detection (LOD) under optimized conditions. However, it failed to overcome the enzymatic sensors’ performances. The ultrasensitive performance was achieved by incorporating a detecting agent in the ink that instilled analyte capture ability. Metal oxides like ZrO2, MnO2, and MgO possessed affinity towards organophosphate (fenitrothion), heavy-metal ion (lead), and nutrient (nitrite). Metal oxides were modified with 3,4-dihydroxylbenzaldehyde (DHBA) – Chitosan (CHIT) to produce well dispersed and uniformly coated stable electrodes. The ZrO2-DHBA-CHIT/NS-AC-MWCNT sensor achieved a remarkable limit of detection of 1.69 nM for FT. The sensor's performance exceeded the enzymatic-based sensors. The commonly found chemical interferents had negligible interference. The sensor produced reliable and satisfactory performance in lake and tap water. The MnO2-DHBA-CHIT/NS-AC-MWCNT/GCE and MgO-DHBA-CHIT/NS-AC-MWCNT/GCE sensors produced an enormous improvement in the sensor performance compared to unmodified electrodes for lead and nitrite detection. The preliminary results on detecting other pollutants like lead and nitrite showed the importance of the methodology in providing a platform for a new class of metal oxide-based sensors. / Thesis / Doctor of Philosophy (PhD) / The growing population and rapid industrial development are affecting the water quality worldwide. The major water pollutants are organophosphates, heavy metal ions, and nutrients. These water pollutants are harmful, and their bioaccumulation poses a major health concern. In the USA alone, water quality issues are predicted to cost $210 billion annually. Therefore, sensors to detect water pollutants are developed to monitor their environmental footprints. Electrochemical sensors are popularly used to detect water pollutants owing to their low-cost and high sensitivity. The objective of this dissertation was to fabricate highly sensitive and specific electrochemical sensors to detect organophosphate (e.g., fenitrothion, FT), heavy metal ion (e.g., lead), and nutrient (e.g., nitrite). The sensors were fabricated with ink based on nanomaterials like carbon nanotubes and detecting agents like metal oxides. The fabricated sensors achieved very high sensitivity and specificity and can detect water pollutants in lake and tap water.

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Sensores eletroquímicos, constituídos de substratos metálicos modificados por metaloporfirinas e de superfícies livres de agentes modificadores, foram desenvolvidos com vistas a aplicações analíticas. Eletrodos de cobre apresentaram ação eletrocatalítica para a oxidação de ácido acetilsalícílico, com possível participação de Cu(III) como mediador na reação de transferência de elétrons. A oxidação de salbutamol sobre eletrodos de carbono vítreo foi conduzida em solução fortemente alcalina, condição na qual a determinação do analito foi viabilizada devido à eliminação de problemas associados à presença de interferentes e ao envenenamento do eletrodo. Superfícies de carbono vítreo, modificadas por adsorção e por eletropolimerização de porfirinas tetrarrutenadas de cobalto (CoTRP) e de níquel (NiTRP), respectivamente, demonstraram a versatilidade que tais compostos oferecem quanto ao modo de recobrimento do sensor, levando à obtenção de efeitos atrativos, tais como eletrocatálise e prevenção de envenenamento. Filmes de CoTRP, cujos sítios ativos são atribuídos ao par redox Ru(III)/Ru(II), mostraram-se úteis na determinação de acetaminofen, facilitando a reação de transferência de elétrons e protegendo o eletrodo contra o envenenamento. A atividade eletrocatalítica de eletrodos modificados por NiTRP, baseados em filmes com centros redox Ni(III)/Ni(II), foi evidente para a oxidação de glicose e de outros compostos orgânicos em meio alcalino. Os sensores desenvolvidos foram adaptados ao sistema BIA (batch injection analysis) para a determinação amperométrica dos analitos em amostras de produtos farmacêuticos. O método BIA mostrou-se adequado para as análises, sendo possível obter sinais transientes de corrente, boa estabilidade e alta dispersão. Os resultados bastante satisfatórios demonstram a aplicabilidade dessa técnica em análises em que alta velocidade e boa precisão são freqüentemente requisitadas. / Electrochemical sensors based on bare and modified electrodes were developed for analytical purposes. Copper electrodes exhibited electrocatalytical action for the acetylsalicylic acid oxidation, with the participation of Cu(III) species as electron-transfer mediators. The salbutamol oxidation at glassy carbon electrodes was carried out in strongly alkaline solution. In such a condition, interferences and electrode fouling were eliminated and the analyte quantification was enabled. Glassy carbon surfaces modified via adsorption and electropolymerization of tetraruthenated cobalt (CoTRP) and nickel (NiTRP) porphyrins, respectively, displayed the usefulness of these compounds for the obtainment of electrocatalysis and fouling prevention. Films based on CoTRP, from what Ru(III) are the active sites, were applicable to acetaminophen analysis by facilitating the electron transfer process and protecting the electrode against fouling. The electrocatalytical activity of modified NiTRP electrodes, based on films with Ni(III)/Ni(II) redox centers, was evident for glucose oxidation and other organic compounds. The sensors were coupled to the BIA (batch injection analysis) system for the amperometric determination of the analytes in pharmaceutical products. BIA was suitable because it presented sharp current response peaks, excellent stability and rapid washing out. The satisfactory results demonstrate the feasibility of such technique for fast analyses with good precision.

Estudos com eletrodos modificados foram conduzidos utilizando dois sistemas porfirínicos supramoleculares diferentes. O primeiro foi baseado na modificação de eletrodo de carbono vítreo com uma porfirina de níquel tetrarrutenada, [NiIITPyP{RuII(bipy)2Cl}4]4+. A modificação do eletrodo foi realizada por meio de sucessivos ciclos voltamétricos em meio alcalino (pH 13), gerando um eletrodo com característica similar a eletrodos modificados com α-Ni(OH)2. A caracterização química do filme formado foi realizada através das técnicas de voltametria cíclica, ressonância paramagnética eletrônica, espectroscopia eletrônica por reflectância e espectroscopia Raman com ensaio espectro-eletroquímico. Os resultados sugerem a formação de um polímero de coordenação, [µ-O2-NiIITPyP{RuII(bipy)2Cl}4]n, composto por subunidades porfirínicas ligadas entre si por pontes µ-peroxo axialmente coordenadas aos átomos de níquel (Ni-O-O-Ni). O crescimento do filme apresentou dependência da alcalinidade do meio pela formação do precursor octaédrico [Ni(OH)2TRPyP]2+ em solução, pela coordenação de OH- nas posições axiais do átomo de níquel. O processo de eletropolimerização indicou a participação de radical hidroxil, gerado por oxidação eletrocatalítica da água nos sítios periféricos da porfirina contendo o complexo de rutênio. O mesmo eletrodo foi aplicado como sensor eletroquímico para análise amperométrica de ácido fólico em comprimidos farmacêuticos. O sensor foi associado a um sistema de Batch Injection Analysis (BIA) alcançando considerável rapidez e baixo limite de detecção. Para as análises das amostras também foi proposto um método para a remoção da lactose, que agia como interferente. O segundo estudo envolveu a modificação de eletrodos de carbono vítreo com diferentes hemoglobinas, naturais (HbA0, HbA2 e HbS) e sintéticas (Hb-PEG5K2, αα-Hb-PEG5K2 e BT-PEG5K4), para a avaliação da eficiência na redução eletrocatalítica de nitrito mediada por FeI-heme. Os filmes foram produzidos pela mistura de soluções das hemoglobinas com brometo de didodecildimetiltrimetilamônio (DDAB), aplicados nas superfícies com consecutiva evaporação, formando filmes estáveis. Os valores de potencial redox para os processos do grupo heme e a sua associação com a disponibilidade do grupo na proteína foram avaliados por voltametria cíclica. Os valores das constantes de velocidade, k, para redução de nitrito foram obtidos por cronoamperometria em -1,1 V (vs Ag/AgCl(KCl 3M)) que foram utilizados para estudo comparativo entre as espécies sintéticas para eventual aplicação clínica. / Studies with modified electrodos were conducted using two different supramolecular porphyrin systems. The first one was based on the modification of glassy carbon electrode with a tetraruthenated nickel porphyrin, [NiIITPyP{RuII(bipy)2Cl}4]4+. The electrode modification was carried out through successive voltemmetric cycles in alkaline media (pH 13), generating an electrode with feature similar to α-Ni(OH)2 modified electrodes. The chemical characterization of this film was performed by cyclic voltammetry, electronic paramagnetic resonance, reflectance electronic spectroscopy and Raman spectroscopy with spectroelectrochemistry assay. The results suggested the formation of a coordination polymer, [µ-O2-NiIITPyP{RuII(bipy)2Cl}4]n, composed by porphyrin subunits linked by µ-peroxo bridges axially coordinated to nickel atoms (Ni-O-O-Ni). The film growth showed dependence of the alkaline media by the formation of octahedral precursor [Ni(OH)2TRPyP]2+ in solution by way of axial coordination of OH- to the nickel atoms. The electropolymerization process showed to have a contribution from hydroxyl radicals, generated by electrocatalytic oxidation of water on the peripheral sites containing the ruthenium complexes. The same electrode was applied as an electrochemical sensor for amperometric analysis of folic acid in pharmaceutical tablets. The sensor was associated to a Bath Injection Analysis (BIA) system, achieving good sampling frequency and low detection limit. For the samples analysis, it was also proposed a method for lactose removal. The second study comprises the modification of glassy carbon electrodes with different hemoglobin species, of natural occurrence (HbA0, HbA2 e HbS) and synthetics (Hb-PEG5K2, αα-Hb-PEG5K2 e BT-PEG5K4) for evaluation of efficiency on electrocatalytic reduction of nitrite mediated by FeI-heme. The films were produced by mixing solutions of the hemoglobins with didecyldimethylammonium bromide (DDAB), applied on the surfaces with following solvent evaporation, forming stable films. The redox potential values for the heme group processes and the heme availability in the protein were evaluated by cyclic voltammetry. The reaction rate constants, k, for nitrite reduction were obtained by chronoamperometry at -1,1 V, which were used for comparative study between the synthetic species for further clinical applications.

Τα συστήματα μοριακής διαγνωστικής έχουν έρθει στο προσκήνιο τα τελευταία χρόνια δίνοντας τη δυνατότητα για αυτοματοποιημένες, αξιόπιστες, γρήγορες και χαμηλού κόστους βιολογικές αναλύσεις. Τέτοια συστήματα χαρακτηρίζονται από σύνθετη λειτουργικότητα, η οποία συνδυάζει πληθώρα ενεργοποιητών και αισθητήρων που συνεργάζονται για την εκτέλεση βιολογικών πρωτοκόλλων. Με βάση τα πρωτόκολλα αυτά και με τη χρήση μικροροϊκών συστημάτων, τα βιολογικά δείγματα και αντιδραστήρια υποβάλλονται σε διάφορα στάδια επεξεργασίας. Κατόπιν της επεξεργασίας τους, τα δείγματα υπό μελέτη καταλήγουν πάνω στην επιφάνεια αισθητήρων, οι οποίοι είναι ειδικά ευαισθητοποιημένοι ώστε να ανιχνεύουν συγκεκριμένες βιολογικές αλληλεπιδράσεις ενδιαφέροντος και να αποκρίνονται μεταβάλλοντας αναλόγως ένα φυσικό μέγεθος, μετρήσιμο από ηλεκτρονικά κυκλώματα. Τα ηλεκτρονικά κυκλώματα ανάγνωσης των αισθητήρων αποτελούν ένα από τα κυριότερα τμήματα ενός συστήματος μοριακής διαγνωστικής, καθώς βάσει της απόκρισης αυτών προκύπτουν τα διαγνωστικά αποτελέσματα. Κατά συνέπεια, αναγνωρίζεται ο σημαντικός ρόλος που κατέχουν στη συνολική αναλυτική διαδικασία. Είναι απαραίτητο οι μετρήσεις που εκτελούν να χαρακτηρίζονται από μεγάλη ακρίβεια με υψηλή διακριτική ικανότητα για κάθε αισθητήριο στοιχείο. Ταυτόχρονα όμως, πρέπει να εξασφαλίζεται και η αξιοπιστία της μέτρησης σε επίπεδο βιολογικής διεργασίας. Σε αυτό το στόχο συντελεί η χρήση συστοιχιών αισθητήρων, με τις οποίες η ίδια μέτρηση μπορεί να εκτελεστεί παράλληλα σε πολλά στοιχεία και συνοδεύεται από μετρήσεις θετικού και αρνητικού ελέγχου. Πάνω στη συστοιχία μπορούν να εκτελεστούν και συμπληρωματικές μετρήσεις περισσότερων δειγμάτων, ώστε τα αποτελέσματα που εξάγονται να δίνουν μια πιο ολοκληρωμένη αναλυτική εικόνα. Υπό αυτό το πρίσμα, οι μεγάλου μεγέθους συστοιχίες αισθητήρων μπορούν να προσφέρουν βέλτιστα αποτελέσματα. Η παρούσα διδακτορική διατριβή επικεντρώνεται στα κυκλώματα ανάγνωσης συστοιχιών χωρητικών και ηλεκτροχημικών αισθητήρων, δύο ευρέως χρησιμοποιούμενων τεχνολογιών αισθητήρων. Η αρχή λειτουργίας των χωρητικών αισθητήρων βασίζεται στο γεγονός ότι οι αλληλεπιδράσεις βιομορίων που μελετούνται ασκούν δυνάμεις και παραμορφώνουν την ευέλικτη μεμβράνη πυριτίου που αποτελεί τον έναν οπλισμό ενός μεταβλητού πυκνωτή. Συνέπεια αυτής της παραμόρφωσης είναι η ανάλογη μεταβολή της χωρητικότητας που παρουσιάζει η μεμβράνη με το υπόστρωμα πυριτίου, μεταβολή που μετράται από το κύκλωμα. Στην περίπτωση των ηλεκτροχημικών αισθητήρων, η αντίστοιχη αλληλεπίδραση βιομορίων, με τη βοήθεια βιομορίων σήμανσης, προκαλεί τη μεταβολή της αγωγιμότητας μεταξύ των ηλεκτροδίων τους. Υπό ελεγχόμενες συνθήκες πόλωσης τάσης, το αναπτυσσόμενο ρεύμα που μετράται αντιστοιχεί στην εξέλιξη του βιολογικού φαινομένου. Ιδιαίτερη έμφαση δίνεται στις δυνατότητες κλιμάκωσης της εκάστοτε αρχιτεκτονικής ώστε να είναι επεκτάσιμη στην ανάγνωση πολύ μεγάλων συστοιχιών αισθητήρων με βέλτιστο τρόπο, διατηρώντας μικρές διαστάσεις για τα κυκλώματα ανάγνωσης. Συγχρόνως, εξασφαλίζεται με διάφορες στρατηγικές η ορθή λήψη μετρήσεων από κάθε στοιχείο, χωρίς την επίδραση από τα υπόλοιπα μέλη της συστοιχίας. Για την ανάγνωση συστοιχιών χωρητικών αισθητήρων σχεδιάστηκε και υλοποιήθηκε ολοκληρωμένο κύκλωμα σε τεχνολογία 0.35 μm, που στον πυρήνα της μέτρησης διαθέτει έναν ταλαντωτή χαλάρωσης με βρόχο υστέρησης ρεύματος. Υποστηρίζεται από προγραμματιζόμενες πηγές ρεύματος διέγερσης ώστε να καλύπτεται ένα ευρύ φάσμα χωρητικοτήτων για τους αισθητήρες. Το σύστημα πολύπλεξης που αναπτύχθηκε για τη διασύνδεση κάθε μέλους από τις συστοιχίες αισθητήρων πάνω στον πυρήνα ανάγνωσης μπορεί να διαχειριστεί πεπλεγμένες συστοιχίες, όπου τα στοιχεία είναι οργανωμένα με κοινές γραμμές και στήλες ηλεκτρικών επαφών στους οπλισμούς τους. Με αυτόν τον τρόπο είναι δυνατή η δημιουργία μεγάλων συστοιχιών με μικρό πλήθος ακροδεκτών διασύνδεσης. Η πρόκληση της ανάγνωσης τέτοιου είδους συστοιχιών έγκειται στις αλληλεπιδράσεις μεταξύ των στοιχείων, λόγω ανεπιθύμητων μονοπατιών στο ρεύμα φόρτισης του ταλαντωτή. Μία πρώτη αντιμετώπιση αυτού του προβλήματος διαφωνίας γίνεται με τη χρήση διακοπτών δύο καταστάσεων στις μονάδες πολύπλεξης, ώστε να ελέγχεται ο τρόπος με τον οποίο διεγείρεται το μετρούμενο καθώς και τα υπόλοιπα στοιχεία κατά τη μέτρηση. Με διαδοχικές μετρήσεις υπό διαφορετικές συνδεσμολογίες στους πολυπλέκτες και με κατάλληλη μαθηματική επεξεργασία, μπορούν να εξαχθούν ακριβείς μετρήσεις για την κατάσταση κάθε αισθητήρα της συστοιχίας. Η στατικότητα του συστήματος κατά τη διάρκεια των διαδοχικών μετρήσεων που είναι προϋπόθεση για το σωστό υπολογισμό των αποτελεσμάτων, βασίζεται στην ιδιαίτερα αργή εξέλιξη των βιολογικών φαινομένων στην επιφάνεια των αισθητήρων. Στα πλαίσια της διατριβής έγινε και ένας επανασχεδιασμός του κυκλώματος ανάγνωσης συστοιχιών, σε επίπεδο σχηματικού και φυσικού σχεδιασμού, του οποίου η λειτουργία επιβεβαιώθηκε με post-layout εξομοιώσεις. Σε αυτή την ανάπτυξη έγινε προσθήκη επιπλέον υπομονάδων και η βελτίωση των υπαρχουσών. Από τα κύρια χαρακτηριστικά αυτού του σχεδιασμού είναι μια μονάδα απομονωτή, που προσφέρει έναν δεύτερο τρόπο αντιμετώπισης του προβλήματος διαφωνίας μεταξύ των στοιχείων, αποτρέποντας το ρεύμα φόρτισης του ταλαντωτή να οδηγηθεί προς μη επιθυμητά στοιχεία. Επιπλέον, οι μονάδες ταλάντωσης που χρησιμοποιεί το επανασχεδιασμένο κύκλωμα είναι δύο, για ταυτόχρονη ανάγνωση αισθητήρων και ταχύτερη σάρωση μεγάλων συστοιχιών, με το εύρος του προγραμματιζόμενου ρεύματος να είναι μεγαλύτερο, καλύπτοντας μεγαλύτερο φάσμα αισθητήρων. Τέλος, αυτή η έκδοση του κυκλώματος έχει πιο αυτόνομο χαρακτήρα, με την ενσωμάτωση ενός υποσυστήματος σειριακής επικοινωνίας και ελέγχου. Για τη δεύτερη τεχνολογία αισθητήρων που καλύπτει η παρούσα διατριβή, των ηλεκτροχημικών αισθητήρων, σχεδιάστηκαν και υλοποιήθηκαν κυκλώματα ανάγνωσης συστοιχιών με χρήση διακριτών στοιχείων, καθώς επίσης και κυκλώματα με το βασικό πυρήνα μέτρησης να υλοποιείται σε ολοκληρωμένη μορφή με τεχνολογία 90 nm. Για τους σχεδιασμούς αυτούς έχει αναπτυχθεί η τεχνική της υβριδικής πολύπλεξης, βάσει της οποίας τα μέλη της συστοιχίας ομαδοποιούνται καταλλήλως, ώστε να επιτευχθούν οι απαιτούμενες επιδόσεις σε ρυθμούς δειγματοληψίας από το κύκλωμα ανάγνωσης, ενώ παράλληλα το μέγεθος του κυκλώματος παραμένει μικρό. Η υβριδική πολύπλεξη συνδυάζει διαδοχική ανάγνωση με παράλληλη ανάγνωση στοιχείων, κάνοντας χρήση πολυπλεκτών και κατάλληλου αριθμού υποσυστημάτων μέτρησης που επαναχρησιμοποιούνται για πολλά αισθητήρια στοιχεία. Η ιδιαιτερότητα που έχουν αυτού του τύπου οι μετρήσεις έγκειται στην απαίτηση για διαρκή πόλωση όλων των στοιχείων χωρίς διακοπή της ροής του ρεύματος μέσω αυτών, που καλύπτεται μέσω ειδικά διαμορφωμένων πολυπλεκτών δύο καταστάσεων οι οποίοι εξασφαλίζουν τις σωστές συνθήκες λειτουργίας. Επιπρόσθετες βελτιώσεις που παρέχει η υλοποίηση του κυκλώματος ανάγνωσης σε μορφή ολοκληρωμένου είναι η δυνατότητα εναλλαγής μεταξύ δύο τύπων κυκλωμάτων μέτρησης, με χρήση ενισχυτή διαντίστασης και ολοκληρωτή. Οι δύο τρόποι μέτρησης χρησιμοποιούνται συμπληρωματικά, ώστε να καλυφθεί μεγάλη δυναμική περιοχή λειτουργίας και γρήγορη απόκριση, αλλά και υψηλή ανάλυση, ανάλογα με τις απαιτήσεις κατά τη διάρκεια της πειραματικής διαδικασίας. Για το χαρακτηρισμό των κυκλωμάτων ανάγνωσης που αναπτύχθηκαν και για τις δύο τεχνολογίες αισθητήρων, έγιναν μετρήσεις με πρότυπα φορτία, καθώς και με συστοιχίες, για να εξαχθούν συμπεράσματα για την απόκρισή τους. Κατόπιν των ελέγχων καλής λειτουργίας των κυκλωμάτων και των μεθόδων που ακολουθούνται, πραγματοποιήθηκαν και επιτυχείς μετρήσεις βιολογικής σημασίας, που επιβεβαιώθηκαν από συστήματα αναφοράς. / Molecular diagnostics systems have come to the forefront in recent years allowing for automated, reliable, rapid and inexpensive bioassays. Such systems are characterized by complex functionality, which combines variety of actuators and sensors that cooperate to perform biological protocols. Based on these protocols and using microfluidic systems, biological samples and reagents are subjected to various processing steps. Following this treatment, the samples under study are placed on the surface of sensors, which are functionalized to detect specific biological interactions of interest and respond accordingly by changing a physical quantity, measurable by electronic circuits. The sensor readout electronic circuits are one of the main parts of a molecular diagnostics system, as the diagnostic results are based on their response. Consequently, it is recognized that they hold an important role in the overall analytical process. It is necessary that the measurements they perform are highly accurate with high resolution for each sensor element. At the same time, the reliability of the measurement at a biological process level must be ensured. To this aim contributes the use of sensor arrays, with which the same measurement can be performed in parallel on many elements and accompanied by positive and negative control measurements. On the array, additional measurements of multiple samples can be performed, so that the output results give a more comprehensive analytical picture. In this light, large sensor arrays can provide optimal results. This thesis focuses on the readout circuitry for capacitive and electrochemical sensor arrays, two widely used sensor technologies. The operating principle of capacitive sensors is based on the fact that the interactions between the biomolecules under study exert forces and deform the flexible silicon film constituting an armature of a variable capacitor. The consequence of this deformation is a proportional change in capacitance between the film and the silicon substrate, a variation measured by the circuit. In the case of electrochemical sensors, the respective interaction of biomolecules, with the aid of labeling biomolecules, causes a change in conductivity between their electrodes. Under controlled bias voltage conditions, the resulting current that is measured corresponds to the progress of the biological phenomenon. Particular emphasis is given to the scalability potential of each architecture, so it can be optimally expanded for reading very large sensor arrays, maintaining small dimensions for the readout circuits. At the same time, through various strategies it is ensured that measurements of each element are properly acquired, without influence from other members in the array. To read out the capacitive sensor arrays an integrated circuit based on a 0.35 μm technology was designed and implemented, which at its measuring core uses a relaxation oscillator with a current hysteresis loop. It is complemented by programmable excitation current sources to cover a wide range of capacitances for the sensors. The multiplexing system that was developed to connect each member of the sensor arrays on the readout core can handle 'entangled' arrays, where the elements are arranged with common lines and columns of electrical contacts at their armatures. In this way it is possible to create large arrays with a small number of interface terminals. The challenge of reading such arrays lies in the interactions between the elements, because of side paths in the oscillator charging current. A first way to address this crosstalk problem is the use of two-state switches in the multiplexing units, in order to control the way in which the measured element is excited, as well as the other array elements, during measurement. Through successive measurements under different connection configurations on the multiplexers and appropriate mathematical processing, accurate measurements for the status of each sensor in the array can be obtained. The measured system can be considered static during successive measurements, which is a prerequisite for the correct calculation of results, due to the very slow progress of biological phenomena on the surface of the sensors. In the course of this thesis, a redesign of the array readout circuit was made, at a schematic and physical layout design level, the function of which was confirmed by post-layout simulations. In this development extra submodules were incorporated and existing ones were improved. One of the main features of this design is a buffer unit, which offers a second way of addressing the crosstalk problem between the elements, by preventing the oscillator charging current to excite undesirable elements. Furthermore, the redesigned circuit uses two oscillation units for simultaneous sensor readout and faster scanning of large arrays, with the range of their programmable current being greater, covering a larger spectrum of sensors. Finally, this version of the circuit has a more autonomous nature, by incorporating a serial communication and control subsystem. For the second sensor technology covered by this thesis, the electrochemical sensors, array readout circuits were designed and implemented using discrete components, as well as circuits with the basic measurement core being implemented in integrated form using a 90 nm technology. For these designs the technique of hybrid multiplexing was developed, whereby the members of the array are grouped appropriately to achieve the required performance in sampling rate from the readout circuit, while the size of the circuit remains small. Hybrid multiplexing combines sequential and parallel element reading, using multiplexers and the appropriate number of measurement subsystems that are reused for many sensing elements. The particularity of this type of measurements is the requirement for continuous biasing of all elements without interruptions in the current flow through them, which is addressed by specially configured two-state multiplexers that ensure the correct operating conditions. Additional enhancements offered by the implementation of the readout circuit in integrated form is the ability to switch between two types of measurement circuits, using a transimpedance amplifier and an integrator. The two modes of measurement are used in complement, to cover a wide operating dynamic range and fast response, and also high resolution, depending on the requirements during the experimental process. For the characterization of the readout circuits developed for both sensor technologies, measurements were made using standard loads, as well as arrays, to draw conclusions about their response. Following the validation of the proper operation of the circuits and methods used, successful measurements of biological significance were made, which were confirmed by reference systems.

In the field of chemical and biological sensors, the increased need for better sensitivity, faster response and higher selectivity during an analysis process, requires the development of more and more efficient transducing sensing layers. In this context, and with the aim to detect small non-electroactive molecules, such as atrazine (ATZ), we designed, characterized and developed sensing layers constituted by functionalized Molecularly Imprinted Conducting Polymers (MICP) and we integrated them into electrochemical and gravimetrical sensors. Starting from acetonitrile pre-polymerization media containing ATZ as template molecules in the presence of thiophene-based functional monomers (FM, namely TMA, TAA, EDOT, TMeOH or Th), differently functionalized and structurally different polythiophene-based FM-MICP films were electrosynthesized onto gold substrates and used for ATZ detection. The sensing properties of FM-MICP layers were shown to result from the presence in their backbones of pre-shaped FM-functionalized imprinted cavities which keep the memory of the targets. Nevertheless, non-specific adsorption onto the surface of the sensing layers takes place systematically, which affects the selectivity of the recognition process. Thanks to surface characterization techniques, we highlighted the influence of the thickness and of the structural properties of the layers on the efficiency of the recognition process. Besides, this latter was shown to operate in the bulk of the polymer matrixes thanks to layers porosity. On another hand, electrochemical measurements correlated with semi-empirical calculations demonstrated the influence of the nature of FM on the strength of the ATZ-FM interaction in the pre-polymerization medium, and then on the number of ATZ molecular imprints and on the sensitivity towards ATZ of the FM-MICP layers. We showed that TAA-MICP, which presents a low limit of detection (10-9 mol L-1) and a large dynamic range (10-8 to 10-4 mol L-1), is the best sensing layer since it offers the best compromise between high level of specific detection of ATZ and low level of non-specific adsorption. Finally, TAA-MICP was used as sensitive layer in an original Electrochemical Surface Acoustic Wave sensor (ESAW) which enabled simultaneous coupled gravimetric and electrochemical measurements.