Semiconducting Polymers for Electronic Biosensors and Biological Interfaces

Bioeletronics aims at the direct coupling of biomolecular function units with standard electronic devices. The main limitations of this field are the material needed to interface soft living entities with hard inorganic devices. Conducting polymers enabled the bridging between these two separate worlds, owing to their biocompatibility, soft nature and the ability to be tailored according to the required application. In particular, the intrinsically conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) is one of the most promising polymers, having an excellent chemical and thermal stability, reversible doping state and high conductivity. This thesis relies on the use of PEDOT:PSS as semiconducting material for biological interfaces and biosensors. In detail, OECTs were demonstrated to be able to real-time monitor growth and detachment of both strong-barrier and no-barrier cells, according to the patterning of the device active area and the selected geometry. Thus, these devices were employed to assess silver nanoparticles (AgNPs) toxicity effects on cell lines, allowing further insights on citrate-coated AgNPs uptake by the cells and their toxic action, while demonstrating no cytotoxic activity of EG6OH-coated AgNPs. Moreover, PEDOT:PSS OECTs were proved to be capable of detecting oxygen dissolved in KCl or even cell culture medium, in the oxygen partial pressure range of 0-5%. Furthermore, PEDOT:PSS OECTs were biofunctionalized to impart specificity on the device sensing capabilities, through a biochemical functionalization strategy, electrically characterized. The resulting devices showed a proof of concept detection of a fundamental cytokine for cells undergoing osteogenic differentiation. Finally, PEDOT:PSS thickness-controlled films were employed as biocompatible, low-impedance and soft interfaces between the animal nerve and a gold electrode. The introduction of the plasticizer polyethylene glycol (PEG) enhanced the elasticity of the polymer, while keeping good conductivity and low-impedance properties. An in-vivo, chronic recording of the renal sympathetic nerve activity in rats demonstrated the efficiency of the device

Charge Carrier Mobility in Organic Mixed Ionic–Electronic Conductors by the Electrolyte-Gated van der Pauw Method

Organic mixed ionic–electronic conductors (OMIECs) combine electronic semiconductor functionality with ionic conductivity, biocompatibility, and electrochemical stability in water and are currently investigated as the active material in devices for bioelectronics, neuromorphic computing, as well as energy conversion and storage. Operation speed of such devices depends on fast electronic transport in OMIECs. However, due to contact resistance problems, reliable measurements of electronic mobility are difficult to achieve in this class of materials. To address the problem, the electrolyte-gated van der Pauw (EgVDP) method is introduced for the simple and accurate determination of the electrical characteristics of OMIEC thin films, independent of contact effects. The technique is applied to the most widespread OMIEC blend, poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonic acid) (PEDOT:PSS). By comparing with organic electrochemical transistor (OECT) measurements, it is found that gate voltage dependent contact resistance effects lead to systematic errors in OECT based transport characterization. These observations confirm that a contact-independent technique is crucial for the proper characterization of OMIECs, and the EgVDP method reveals to be a simple, elegant, but effective technique for this scope

AC amplification gain in organic electrochemical transistors for impedance-based single cell sensors

Research on electrolyte-gated and organic electrochemical transistor (OECT) architectures is motivated by the prospect of a highly biocompatible interface capable of amplifying bioelectronic signals at the site of detection. Despite many demonstrations in these directions, a quantitative model for OECTs as impedance biosensors is still lacking. We overcome this issue by introducing a model experiment where we simulate the detection of a single cell by the impedance sensing of a dielectric microparticle. The highly reproducible experiment allows us to study the impact of transistor geometry and operation conditions on device sensitivity. With the data we rationalize a mathematical model that provides clear guidelines for the optimization of OECTs as single cell sensors, and we verify the quantitative predictions in an in-vitro experiment. In the optimized geometry, the OECT-based impedance sensor allows to record single cell adhesion and detachment transients, showing a maximum gain of 20.2±0.9 dB with respect to a single electrode-based impedance sensor

Design of an electrochemically gated organic semiconductor for pH sensing

Since the development of potentiometric ion-selective electrodes, remarkable steps have been taken towards progressive simplification and improved robustness of pH sensing probes. In particular, the design of compact sensing architectures using solid-state components holds great potential for portable and wearable applications. Here we report the development of an electrochemically gated device for pH detection, combining the robustness of potentiometric-like transduction with an extremely simple and integrated geometry requiring no reference. The sensor is a two-point probe device comprising two thin polymeric films, i.e. a charge transport layer and a pH-sensitive layer, and exhibits a sensitivity of (8.3 ± 0.2) × 10−3 pH unit−1 in the pH range from 2 to 7. Thanks to the versatility and robustness of the optimised design, a textile pH sensor was fabricated whose performance is comparable with that of glass sensors

Oxygen Gas Sensing Using a Hydrogel-Based Organic Electrochemical Transistor for Work Safety Applications

open8noOxygen depletion in confined spaces represents one of the most serious and underestimated dangers for workers. Despite the existence of several commercially available and widely used gas oxygen sensors, injuries and deaths from reduced oxygen levels are still more common than for other hazardous gases. Here, we present hydrogel-based organic electrochemical transistors (OECTs) made with the conducting polymer poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) as wearable and real-time oxygen gas sensors. After comparing OECT performances using liquid and hydrogel electrolytes, we identified the best PEDOT:PSS active layer and hydrogel coating (30 µm) combination for sensing oxygen in the concentration range of 13–21% (v/v), critical for work safety applications. The fast O2 solubilization in the hydrogel allowed for gaseous oxygen transduction in an electrical signal thanks to the electrocatalytic activity of PEDOT:PSS, while OECT architecture amplified the response (gain ̴ 104). OECTs proved to have comparable sensitivities if fabricated on glass and thin plastic substrates, (−12.2 ± 0.6) and (−15.4 ± 0.4) µA/dec, respectively, with low power consumption (<40 µW). Sample bending does not influence the device response, demonstrating that our real-time conformable and lightweight sensor could be implemented as a wearable, noninvasive safety tool for operators working in potentially hazardous confined spaces.The work was supported by the European Union FESR FSE, PON Research and Innovation 2014-2020 and FSC, project number ARS01-00996 "TEXT-STYLENuovi tessuti intelligenti e sostenibilimultisettoriali per il design creative e stileMade-in-Italy" and by the Italian Ministry of Economic Development 2020-Project "AlmaMater patents-Monitoraggio in continuo di pH e idratazione-MIRAGE".openFrancesco Decataldo, Filippo Bonafè, Federica Mariani, Martina Serafini, Marta Tessarolo, Isacco Gualandi, Erika Scavetta, Beatrice FraboniFrancesco Decataldo, Filippo Bonafè, Federica Mariani, Martina Serafini, Marta Tessarolo, Isacco Gualandi, Erika Scavetta, Beatrice Frabon

Smart Bandaid Integrated with Fully Textile OECT for Uric Acid Real-Time Monitoring in Wound Exudate

: Hard-to-heal wounds (i.e., severe and/or chronic) are typically associated with particular pathologies or afflictions such as diabetes, immunodeficiencies, compression traumas in bedridden people, skin grafts, or third-degree burns. In this situation, it is critical to constantly monitor the healing stages and the overall wound conditions to allow for better-targeted therapies and faster patient recovery. At the moment, this operation is performed by removing the bandages and visually inspecting the wound, putting the patient at risk of infection and disturbing the healing stages. Recently, new devices have been developed to address these issues by monitoring important biomarkers related to the wound health status, such as pH, moisture, etc. In this contribution, we present a novel textile chemical sensor exploiting an organic electrochemical transistor (OECT) configuration based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) for uric acid (UA)-selective monitoring in wound exudate. The combination of special medical-grade textile materials provides a passive sampling system that enables the real-time and non-invasive analysis of wound fluid: UA was detected as a benchmark analyte to monitor the health status of wounds since it represents a relevant biomarker associated with infections or necrotization processes in human tissues. The sensors proved to reliably and reversibly detect UA concentration in synthetic wound exudate in the biologically relevant range of 220-750 μM, operating in flow conditions for better mimicking the real wound bed. This forerunner device paves the way for smart bandages integrated with real-time monitoring OECT-based sensors for wound-healing evaluation

PEDOT:PSS: un polimero conduttivo organico per lo studio dell'integrità del tessuto cellulare

Questa tesi si inserisce nel campo della Bioelettronica Organica con lo scopo di utilizzare dei transistor elettrochimici (OECT) organici basati sul polimero conduttivo PEDOT:PSS per rilevare l’integrità di un tessuto cellulare e come biosensori di analiti in soluzione. Nella prima parte dell’elaborato, si spiegano le proprietà ed il trasporto di carica dei polimeri coniugati concentrandosi sulle caratteristiche fisico chimiche del PEDOT:PSS, seguito da una trattazione analitica del principio di funzionamento di un OECT. La seconda parte, si concentra sul lavoro sperimentale partendo da una descrizione dei processi di fabbricazione degli OECT, dei metodi di caratterizzazione utilizzati e della progettazione del set-up sperimentale per permettere le misure elettriche nell’incubatore cellulare. In seguito, viene dimostrato l’uso di un OECT completamente a base di PEDOT:PSS come sensore di un neurotrasmettitore (dopamina). In parallelo, il lavoro si è concentrato sull’ottimizzazione dei transistor in termini di formulazione di PEDOT:PSS e di geometria del dispositivo per ottenere tempi di spegnimento veloci compatibili con le risposte cellulari (<300ms). In fase di preparazione alle misure con le cellule si è valutato la funzionalità dell’OECT nelle condizioni di coltura cellulare dimostrando una buona stabilità dei dispositivi. Inoltre, sono stati progettati degli studi di simulazione tramite una membrana porosa per prevedere le risposte dei transistor in presenza di un tessuto cellulare. Partendo dall’esito positivo dei test preliminari, il lavoro si è concluso con il primo esperimento con le cellule tumorali HeLa, in cui si è monitorata la crescita cellulare con immagini ottiche correlate alle misure elettriche. I primi risultati confermano la biocompatibilità dei dispositivi e una risposta elettrica degli OECTs alla presenza delle cellule, aprendo la possibilità di utilizzare questi dispositivi per futuri esperimenti anche con diversi tipi di cellule

Studio di transistor elettrochimici e loro applicazioni

In questa tesi, utilizzando le particolari proprietà del polimero conduttivo poli(3,4-etilenediossitiofene) drogato con polistirene sulfonato , o PEDOT:PSS, sono stati realizzati dei transistor elettrochimici organici (OECTs), in cui il gate e canale source-drain sono stati realizzati depositando su substrato di vetro film sottili di questo polimero. I dispositivi realizzati sono stati caratterizzati, per comprenderne meglio le funzionalità e le proprietà per possibili applicazioni future, in particolare come sensori di glucosio. Il PEDOT:PSS è uno dei materiali più studiati per applicazioni della bioelettronica in virtù della sua grande stabilità chimica e termica, della reversibilità del suo processo di drogaggio, della grande conducibilità e delle sue proprietà elettrochimiche, nonché della sua attività in un vasto range di pH. Vengono trattate nell’elaborato anche le tecniche di deposizione di questo polimero per la creazione di film sottili, necessari per le varie applicazioni nell’ambito della bioelettronica organica, la quale si propone di unire la biologia e l’elettronica in un mutuale scambio di informazioni e segnali. Questa interazione si sta verificando soprattutto nel campo sanitario, come si può evincere dagli esempi riportati nella trattazione. Si conclude la parte teorica con una descrizione degli OECTs: viene spiegata la loro struttura, la capacità di connettere conducibilità ionica ed elettronica e il loro funzionamento, inserendo anche un confronto con i FET (“Field Effect Transistor”), per agevolare la comprensione dei meccanismi presenti in questi strumenti. Per la parte sperimentale si presenta invece una descrizione dettagliata dei procedimenti, degli strumenti e degli accorgimenti usati nel fabbricare i transistor sui quali si è lavorato in laboratorio, riportando anche una piccola esposizione sulle principali misure effettuate: curve caratterische I–V, transcaratteristiche e misure di corrente nel tempo sono le principali acquisizioni fatte per studiare i dispositivi. E’ stata studiata la diversa risposta degli OECTs al variare della concentrazione di PBS in soluzione, mostrando un generale rallentamento dei processi e una diminuzione della capacità di modificare la corrente source-drain al calare della concentrazione. In seguito, è stato effettuato un confronto tra transistor appena fatti e gli stessi analizzati dopo un mese, osservando una riduzione della corrente e quindi della conducibilità, seppur senza una modifica qualitativa delle curve caratteristiche (che mantengono il loro andamento). Per quanto riguarda la possibilità di usare questi dispositivi come sensori di glucosio, si introduce uno studio preliminare sulla risposta di un transistor, il cui gate è stato funzionalizzato con ferrocene, alla presenza di glucosio e glucosio ossidasi, un enzima necessario al trasferimento di elettroni, nella soluzione elettrolitica, seppur con qualche difficoltà, per via della mancanza di informazioni sui parametri da utilizzare e il range in cui compiere le misure (tuttora oggetto di ricerca)

Oxygen Gas Sensing Using a Hydrogel-Based Organic Electrochemical Transistor for Work Safety Applications

Oxygen depletion in confined spaces represents one of the most serious and underestimated dangers for workers. Despite the existence of several commercially available and widely used gas oxygen sensors, injuries and deaths from reduced oxygen levels are still more common than for other hazardous gases. Here, we present hydrogel-based organic electrochemical transistors (OECTs) made with the conducting polymer poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) as wearable and real-time oxygen gas sensors. After comparing OECT performances using liquid and hydrogel electrolytes, we identified the best PEDOT:PSS active layer and hydrogel coating (30 &micro;m) combination for sensing oxygen in the concentration range of 13&ndash;21% (v/v), critical for work safety applications. The fast O2 solubilization in the hydrogel allowed for gaseous oxygen transduction in an electrical signal thanks to the electrocatalytic activity of PEDOT:PSS, while OECT architecture amplified the response (gain ~ 104). OECTs proved to have comparable sensitivities if fabricated on glass and thin plastic substrates, (&minus;12.2 &plusmn; 0.6) and (&minus;15.4 &plusmn; 0.4) &micro;A/dec, respectively, with low power consumption (&lt;40 &micro;W). Sample bending does not influence the device response, demonstrating that our real-time conformable and lightweight sensor could be implemented as a wearable, noninvasive safety tool for operators working in potentially hazardous confined spaces