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MARCELLO BERTO

Ricercatore t.d. art. 24 c. 3 lett. A
Dipartimento di Scienze della Vita sede ex Chimica V.Campi 103

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Pubblicazioni

2024 - How Biorecognition Affects the Electronic Properties of Reduced Graphene Oxide in Electrolyte‐Gated Transistor Immunosensors [Articolo su rivista]
Sensi, Matteo; de Oliveira, Rafael Furlan; Berto, Marcello; Paradisi, Alessandro; Greco, Pierpaolo; Bortolotti, Carlo Augusto; Samorì, Paolo; Biscarini, Fabio
abstract

Ambipolar electrolyte-gated transistors (EGTs) based on reduced graphene oxide (rGO) have been demonstrated as ultra-sensitive and highly specific immunosensors. However, the physics and chemistry ruling the device operation are still not fully unraveled. In this work, the aim is to elucidate the nature of the observed sensitivity of the device. Toward this aim, a physical–chemical model that, coupled with the experimental characterization of the rGO-EGT, allows one to quantitatively correlate the biorecognition events at the gate electrode and the electronic properties of rGO-EGT is proposed. The equilibrium of biorecognition occurring at the gate electrode is shown to determine the apparent charge neutrality point (CNP) of the rGO channel. The multiparametric analysis of the experimental transfer characteristics of rGO-EGT reveals that the recognition events modulate the CNP voltage, the excess carrier density Δn, and the quantum capacitance of rGO. This analysis also explains why hole and electron carrier mobilities, interfacial capacitance, the curvature of the transfer curve, and the transconductances are insensitive to the target concentration. The understanding of the mechanisms underlying the transistor transduction of the biorecognition events is key for the interpretation of the response of the rGO-EGT immunosensors and to guide the design of novel and more sensitive devices.

2023 - A PETase enzyme synthesised in the chloroplast of the microalga Chlamydomonas reinhardtii is active against post-consumer plastics [Articolo su rivista]
Di Rocco, G.; Taunt, H. N.; Berto, M.; Jackson, H. O.; Piccinini, D.; Carletti, A.; Scurani, G.; Braidi, N.; Purton, S.
abstract

Polyethylene terephthalate hydrolases (PETases) are a newly discovered and industrially important class of enzymes that catalyze the enzymatic degradation of polyethylene terephatalate (PET), one of the most abundant plastics in the world. The greater enzymatic efficiencies of PETases compared to close relatives from the cutinase and lipase families have resulted in increasing research interest. Despite this, further characterization of PETases is essential, particularly regarding their possible activity against other kinds of plastic. In this study, we exploited for the first time the use of the microalgal chloroplast for more sustainable synthesis of a PETase enzyme. A photosynthetic-restoration strategy was used to generate a marker-free transformant line of the green microalga Chlamydomonas reinhardtii in which the PETase from Ideonella sakaiensis was constitutively expressed in the chloroplast. Subsequently, the activity of the PETase against both PET and post-consumer plastics was investigated via atomic force microscopy, revealing evidence of degradation of the plastics.

2023 - Reduced Graphene Oxide Electrolyte-Gated Transistor Immunosensor with Highly Selective Multiparametric Detection of Anti-Drug Antibodies [Articolo su rivista]
Sensi, M.; de Oliveira, R. F.; Berto, M.; Palmieri, M.; Ruini, E.; Livio, P. A.; Conti, A.; Pinti, M.; Salvarani, C.; Cossarizza, A.; Cabot, J. M.; Ricart, J.; Casalini, S.; Gonzalez-Garcia, M. B.; Fanjul-Bolado, P.; Bortolotti, C. A.; Samori, P.; Biscarini, F.
abstract

The advent of immunotherapies with biological drugs has revolutionized the treatment of cancers and auto-immune diseases. However, in some patients, the production of anti-drug antibodies (ADAs) hampers the drug efficacy. The concentration of ADAs is typically in the range of 1-10 pm; hence their immunodetection is challenging. ADAs toward Infliximab (IFX), a drug used to treat rheumatoid arthritis and other auto-immune diseases, are focussed. An ambipolar electrolyte-gated transistor (EGT) immunosensor is reported based on a reduced graphene oxide (rGO) channel and IFX bound to the gate electrode as the specific probe. The rGO-EGTs are easy to fabricate and exhibit low voltage operations (& LE; 0.3 V), a robust response within 15 min, and ultra-high sensitivity (10 am limit of detection). A multiparametric analysis of the whole rGO-EGT transfer curves based on the type-I generalized extreme value distribution is proposed. It is demonstrated that it allows to selectively quantify ADAs also in the co-presence of its antagonist tumor necrosis factor alpha (TNF-alpha), the natural circulating target of IFX.

2022 - Detection of Neurofilament Light Chain with Label-Free Electrolyte-Gated Organic Field-Effect Transistors [Articolo su rivista]
Solodka, K.; Berto, M.; Ferraro, D.; Menozzi, C.; Borsari, M.; Bortolotti, C. A.; Biscarini, F.; Pinti, M.
abstract

Neurofilaments are structural scaffolding proteins of the neuronal cytoskeleton. Upon axonal injury, the neurofilament light chain (NF-L) is released into the interstitial fluid and eventually reaches the cerebrospinal fluid and blood. Therefore, NF-L is emerging as a biomarker of neurological disorders, including neurodegenerative dementia, Parkinson's disease, and multiple sclerosis. It is challenging to quantify NF-L in bodily fluids due to its low levels. This work reports the detection of NF-L in aqueous solutions with an organic electronic device. The biosensor is based on the electrolyte-gated organic field-effect transistor (EGOFET) architecture and can quantify NF-L down to sub-pM levels; thanks to modification of the device gate with anti-NF-L antibodies imparted with potentially controlled orientation. The response is fitted to the Guggenheim–Anderson–De Boer adsorption model to describe NF-L adsorption at the gate/electrolyte interface, to consider the formation of a strongly adsorbed protein layer bound to the antibody and the formation of weakly bound NF-L multilayers, an interpretation which is also backed up by morphological characterization via atomic force microscopy. The label-free, selective, and rapid response makes this EGOFET biosensor a promising tool for the diagnosis and monitoring of neuronal damages through the detection of NF-L in physio-pathological ranges.

2022 - Monitoring DNA Hybridization with Organic Electrochemical Transistors Functionalized with Polydopamine [Articolo su rivista]
Sensi, M.; Migatti, G.; Beni, V.; D'Alvise, T. M.; Weil, T.; Berto, M.; Greco, P.; Imbriano, C.; Biscarini, F.; Bortolotti, C. A.
abstract

Organic electrochemical transistors (OECTs) are finding widespread application in biosensing, thanks to their high sensitivity, broad dynamic range, and low limit of detection. An OECT biosensor requires the immobilization of a biorecognition probe on the gate, or else on the channel, through several, often lengthy, chemical steps. In this work, a fast and straightforward way to functionalize the carbon gate of a fully screen-printed OECT by means of a polydopamine (PDA) film is presented. By chemical immobilization of an amine-terminated single-stranded oligonucleotide, containing the HSP70 promoter CCAAT sequence, on the PDA film, the detection of the complementary DNA strand is demonstrated. Furthermore, the specificity of the developed genosensor is assessed by comparing its response to the fully complementary strand with the one to partially complementary and noncomplementary oligonucleotides. The developed sensor shows a theoretical limit of detection (LOD) of 100 × 10−15 m and a dynamic range over four orders of magnitude.

2021 - Anti-drug antibody detection with label-free electrolyte-gated organic field-effect transistors [Articolo su rivista]
Sensi, Matteo; Berto, Marcello; Gentile, Sara; Pinti, Marcello; Conti, Andrea; Pellacani, Giovanni; Salvarani, Carlo; Cossarizza, Andrea; Bortolotti, Carlo Augusto; Biscarini, Fabio
abstract

The efficacy of immunotherapy can be undermined by the development of an immune response against a drug/antibody mediated by anti-drug antibodies (ADAs) in treated patients. We present the first label-free EGOFET immunosensor that integrates a biological drug, Nivolumab (Opdivo©), as a specific recognition moiety to quantitatively and selectively detect ADAs against the drug. The limit of detection is 100 fM. This demonstration is a prelude to the detection of ADAs in a clinical setting in the treatment of different pathologies, and it also enables rapid screening of biological drugs for immunogenicity.

2021 - Green Fabrication of (6,5)Carbon Nanotube/Protein Transistor Endowed with Specific Recognition [Articolo su rivista]
Berto, M.; Di Giosia, M.; Giordani, M.; Sensi, M.; Valle, F.; Alessandrini, A.; Menozzi, C.; Cantelli, A.; Gazzadi, G. C.; Zerbetto, F.; Calvaresi, M.; Biscarini, F.; Bortolotti, C. A.
abstract

A general single-step approach is introduced for the green fabrication of hybrid biosensors from water dispersion. The resulting device integrates the semiconducting properties of a carbon nanotube (CNT) and the functionality of a protein. In the initial aqueous phase, the protein (viz., lysozyme [LZ]) disperses the (6,5)CNT. Drop-casting of the dispersion on a test pattern (a silicon wafer with interdigitated Au source and drain electrodes) yields a fully operating, robust, electrolyte-gated transistor (EGT) in one step. The EGT response to biorecognition is then assessed using the LZ inhibitor N-acetyl glucosamine trisaccharide. Analysis of the output signal allows one to extract a protein-substrate binding constant in line with values reported for the free (without CNT) system. The methodology is robust, easy to optimize, redirectable toward different targets and sets the grounds for a new class of CNT-protein biosensors that overcome many limitations of the technology of fabrication of CNT biosensors.

2021 - Physical insights from the Frumkin isotherm applied to electrolyte gated organic transistors as protein biosensors [Articolo su rivista]
Manco Urbina, Pamela Allison; Berto, Marcello; Greco, Pierpaolo; Sensi, Matteo; Borghi, Simone; Borsari, Marco; Bortolotti, Carlo Augusto; Biscarini, Fabio
abstract

2020 - A Bacterial Photosynthetic Enzymatic Unit Modulating Organic Transistors with Light [Articolo su rivista]
Di Lauro, M.; la Gatta, S.; Bortolotti, C. A.; Beni, V.; Parkula, V.; Drakopoulou, S.; Giordani, M.; Berto, M.; Milano, F.; Cramer, T.; Murgia, M.; Agostiano, A.; Farinola, G. M.; Trotta, M.; Biscarini, F.
abstract

The photochemical core of every photosynthetic apparatus is the reaction center, a transmembrane enzyme that converts photons into charge-separated states across the biological membrane with an almost unitary quantum yield. A light-responsive organic transistor architecture, which converts light into electrical current by exploiting the efficiency of this biological machinery, is presented. Proper surface tailoring enables the integration of the bacterial reaction center as photoactive element in organic transistors, allowing the transduction of its photogenerated voltage into photomodulation of the output current up to two orders of magnitude. This device architecture, termed light-responsive electrolyte-gated organic transistor, is the prototype of a new generation of low-power hybrid bio-optoelectronic organic devices.

2020 - Flexible Printed Organic Electrochemical Transistors for the Detection of Uric Acid in Artificial Wound Exudate [Articolo su rivista]
Galliani, M.; Diacci, C.; Berto, M.; Sensi, M.; Beni, V.; Berggren, M.; Borsari, M.; Simon, D. T.; Biscarini, F.; Bortolotti, C. A.
abstract

Low-cost, minimally invasive sensors able to provide real-time monitoring of wound infection can enable the optimization of healthcare resources in chronic wounds management. Here, a novel printed organic electrochemical transistors (OECT) biosensor for monitoring uric acid (UA), a bacterial infection biomarker in wounds, is demonstrated in artificial wound exudate. The sensor exploits the enzymatic conversion of UA to 5-hydroxyisourate, catalyzed by Uricase entrapped in a dual-ionic-layer hydrogel membrane casted onto the gate. The sensor response is based on the catalytic oxidation of the hydrogen peroxide, generated as part of the Uricase regeneration process, at the Pt modified gate. The proposed dual membrane avoids the occurrence of nonspecific faradic reactions as, for example, the direct oxidation of UA or other electroactive molecules that would introduce a potentially false negative response. The biosensor is robust and its response is reproducible both in phosphate buffer saline and in complex solutions mimicking the wound exudate. The sensor has a high sensitivity in the range encompassing the pathological levels of UA in wounds (<200 μm) exhibiting a limit of detection of 4.5 μm in artificial wound exudate. All these characteristics make this OECT-based biosensor attractive for wound monitoring interfaced to the patient.

2020 - Harnessing Selectivity and Sensitivity in Electronic Biosensing: A Novel Lab-on-Chip Multigate Organic Transistor [Articolo su rivista]
Parkula, Vitaliy; Berto, Marcello; Diacci, Chiara; Patrahau, Bianca; Di Lauro, Michele; Kovtun, Alessandro; Liscio, Andrea; Sensi, Matteo; Samorì, Paolo; Greco, Pierpaolo; Bortolotti, Carlo A; Biscarini, Fabio
abstract

Electrolyte gated organic transistors can operate as powerful ultrasensitive biosensors, and efforts are currently devoted to devising strategies for reducing the contribution of hardly avoidable, nonspecific interactions to their response, to ultimately harness selectivity in the detection process. We report a novel lab-on-a-chip device integrating a multigate electrolyte gated organic field-effect transistor (EGOFET) with a 6.5 μL microfluidics set up capable to provide an assessment of both the response reproducibility, by enabling measurement in triplicate, and of the device selectivity through the presence of an internal reference electrode. As proof-of-concept, we demonstrate the efficient operation of our pentacene based EGOFET sensing platform through the quantification of tumor necrosis factor alpha with a detection limit as low as 3 pM. Sensing of inflammatory cytokines, which also include TNFα, is of the outmost importance for monitoring a large number of diseases. The multiplexable organic electronic lab-on-chip provides a statistically solid, reliable, and selective response on microliters sample volumes on the minutes time scale, thus matching the relevant key-performance indicators required in point-of-care diagnostics.

2020 - Neuromorphic Organic Devices that Specifically Discriminate Dopamine from Its Metabolites by Nonspecific Interactions [Articolo su rivista]
Giordani, M.; Sensi, M.; Berto, M.; Di Lauro, M.; Bortolotti, C. A.; Gomes, H. L.; Zoli, M.; Zerbetto, F.; Fadiga, L.; Biscarini, F.
abstract

Specific detection of dopamine (DA) is achieved with organic neuromorphic devices with no specific recognition function in an electrolyte solution. The response to voltage pulses consists of amplitude-depressed current spiking mimicking the short-term plasticity (STP) of synapses. An equivalent circuit hints that the STP timescale of the device arises from the capacitance and resistance of the poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) in series with the electrolyte resistance. Both the capacitance and resistance of PEDOT:PSS change with solution compositions. Dose curves are constructed from the STP timescale for each DA metabolite from pM to mM range of concentrations. The STP response of DA is distinctive from the other metabolites even when differences are by one functional group. Both STP and sensitivity to DA are larger across the patho-physiological range with respect to those to DA metabolites. Density functional theory calculations hint to a stronger hydrogen bond pattern of DA ammonium compared to cationic metabolites. The exponential correlation between STP and the binding energy of DA metabolites interacting with PEDOT:PSS indicates that the slow dynamics of ionic species in and out PEDOT:PSS is the origin of the neuromorphic STP. The sensing framework discriminates differences of nonspecific interactions of few kcal mol−1, corresponding to one functional group in the molecule.

2020 - Neuromorphic Organic Devices: Neuromorphic Organic Devices that Specifically Discriminate Dopamine from Its Metabolites by Nonspecific Interactions (Adv. Funct. Mater. 28/2020) [Altro]
Giordani, Martina; Sensi, Matteo; Berto, Marcello; Di Lauro, Michele; Bortolotti, Carlo Augusto; Gomes, Henrique Leonel; Zoli, Michele; Zerbetto, Francesco; Fadiga, Luciano; Biscarini, Fabio
abstract

2020 - Photovoltage generation in enzymatic bio-hybrid architectures [Articolo su rivista]
Di Lauro, M.; Buscemi, G.; Bianchi, M.; de Salvo, A.; Berto, M.; Carli, S.; Farinola, G. M.; Fadiga, L.; Biscarini, F.; Trotta, M.
abstract

Most of the photochemical activity of bacterial photosynthetic apparatuses occurs in the reaction center, a transmembrane protein complex which converts photons into charge-separated states across the membrane with a quantum yield close to unity, fuelling the metabolism of the organism. Integrating the reaction center from the bacterium Rhodobacter sphaeroides onto electroactive surfaces, it is possible to technologically exploit the efficiency of this natural machinery to generate a photovoltage upon Near Infra-Red illumination, which can be used in electronic architectures working in the electrolytic environment such as electrolyte-gated organic transistors and bio-photonic power cells. Here, photovoltage generation in reaction center-based bio-hybrid architectures is investigated by means of chronopotentiometry, isolating the contribution of the functionalisation layers and defining novel surface functionalization strategies for photovoltage tuning.

2019 - Biosensing with Electrolyte Gated Organic Field Effect Transistors [Capitolo/Saggio]
Bortolotti, Carlo Augusto; Berto, Marcello; Sensi, Matteo; DI LAURO, Michele; Biscarini, Fabio
abstract

Electrolyte Gated Organic Field Effect Transistors (EGOFETs) are rapidly emerging as novel players in the field of biosensing: they allow ultra-sensitive, label-free and fast response, and can be employed to sense very diverse analytes, from small molecules to large multimeric proteins. Here, we present the current level of understanding of the working mechanism of EGOFETs, and review some of the most recent and relevant applications as sensors for healthcare and life sciences, discussing advantages and limitations of this technology. EGOFETs appear as a powerful sensing platform that can be readily adapted to the detection of a wide range of biologically relevant species.

2019 - Label free detection of plant viruses with organic transistor biosensors [Articolo su rivista]
Berto, Marcello; Vecchi, Eugenia; Baiamonte, Luca; Condò, Carla; Sensi, Matteo; Di Lauro, Michele; Sola, Marco; De Stradis, Angelo; Biscarini, Fabio; Minafra, Angelantonio; Bortolotti, Carlo Augusto
abstract

Plum Pox Virus (PPV) is the pathogen responsible for Sharka, a highly infectious disease affecting stone fruit trees and causing severe economic damages, which can be only contained through early-detection and frequent monitoring. We propose a bioelectronic PPV biosensor, based on a electrolyte-gated organic field-effect transistor (EGOFET), for the specific detection of PPV in plant extracts with a sub ng/ml detection limit. The sensing unit of the biosensor is based on anti-PPV antibodies, uniformly oriented on the gold gate electrode by using a sub-monolayer of Protein G. The sensitivity and dynamic range of the EGOFET-based biosensor are comparable to those of commercially available platforms for detection of plant pathogens. This novel electronic immunosensor is compatible with low-cost fabrication procedures and can be easily reconfigured into a fully portable device to be operated in greenhouse and in the field orchards.

2019 - Modulating the Faradic Operation of All-Printed Organic Electrochemical Transistors by Facile in Situ Modification of the Gate Electrode [Articolo su rivista]
Sensi, Matteo; Berto, Marcello; Candini, Andrea; Liscio, Andrea; Cossarizza, Andrea; Beni, Valerio; Biscarini, Fabio; Bortolotti, Carlo Augusto
abstract

Organic electrochemical transistors (OECTs) operated in the faradic regime were shown as outperforming transducers of bioelectric signals in vitro and in vivo. Fabrication by additive manufacturing techniques fosters OECTs as ideal candidates for point-of-care applications, as well as imposes limitations on the choice of materials and their processing conditions. Here, we address the question of how the response of fully printed OECTs depends on gate electrode material. Toward this end, we investigate the redox processes underlying the operation of OECTs under faradic regime, to show OECTs with carbon gate (C-gate) that exhibit no current modulation gate voltages <1.2 V. This is a hallmark that no interference with the faradic operation of the device enabled by redox processes occurs when operating C-gate OECTs in the low-voltage range as label-free biosensors for the detection of electroactive (bio)molecules. To tune the faradic response of the device, we electrodeposited Au on the carbon gate (Au-C-gate), obtaining a device that operates at lower gate voltage values than C-gate OECT. The presence of gold on the gate allowed further modification of the electrical performances by functionalization of the Au-C-gate with different self-assembled monolayers by fast potential-pulse-assisted method. Moreover, we show that the presence in the electrolyte solution of an external redox probe can be used to drive the faradic response of both C- and Au-C-gate OECTs, impacting on the gate potential window that yields effective drain current modulation. The results presented here suggest possible new strategies for controlling the faradic operation regime of OECTs sensors by chemical modification of the gate surface.

2018 - EGOFET Peptide Aptasensor for Label-Free Detection of Inflammatory Cytokines in Complex Fluids [Articolo su rivista]
Berto, Marcello; Diacci, Chiara; D'Agata, Roberta; Pinti, Marcello; Bianchini, Elena; Lauro, Michele Di; Casalini, Stefano; Cossarizza, Andrea; Berggren, Magnus; Simon, Daniel; Spoto, Giuseppe; Biscarini, Fabio; Bortolotti, Carlo A.
abstract

Organic electronic transistors are rapidly emerging as ultrahigh sensitive label-free biosensors suited for point-of-care or in-field deployed applications. Most organic biosensors reported to date are based on immunorecognition between the relevant biomarkers and the immobilized antibodies, whose use is hindered by large dimensions, poor control of sequence, and relative instability. Here, an electrolyte-gated organic field effect transistor (EGOFET) biosensor where the recognition units are surface immobilized peptide aptamers (Affimer proteins) instead of antibodies is reported. Peptide aptasensor for the detection of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) with a 1 × 10−12 M limit of detection is demonstrated. Ultralow sensitivity is met even in complex solutions such as cell culture media containing 10% serum, demonstrating the remarkable ligand specificity of the device. The device performances, together with the simple one-step immobilization strategy of the recognition moieties and the low operational voltages, all prompt EGOFET peptide aptasensors as candidates for early diagnostics and monitoring at the point-of-care.

2018 - Exploiting interfacial phenomena in organic bioelectronics: Conformable devices for bidirectional communication with living systems [Articolo su rivista]
Di Lauro, Michele; Benaglia, Simone; Berto, Marcello; Bortolotti, Carlo A.; Zoli, Michele; Biscarini, Fabio
abstract

A novel fully organic bioelectronic device is presented and validated as electronic transducer and current stimulator for brain implants. The device integrates polymeric electrodes made of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on paper thin foils, resulting in a high surface-to-volume ratio architecture that exhibits high sensitivity to interfacial ionic transport phenomena. The prototyping technique herein presented yields devices for the bidirectional communication with biological systems whose dimensionality can be controlled according to the desired application. Transduction of ultra-low local-field potentials and delivery of voltage pulse-trains alike those used in deep-brain stimulation are herein assessed, paving the way towards novel theranostic strategies for the treatment of Parkinson's Disease and other severe neurodegenerative and/or traumatic pathologies of the central nervous system.

2018 - Label free urea biosensor based on organic electrochemical transistors [Articolo su rivista]
Berto, Marcello; Diacci, Chiara; Theuer, Lorenz; Di Lauro, Michele; Simon, Daniel T.; Berggren, Magnus; Biscarini, Fabio; Beni, Valerio; Bortolotti, Carlo A.
abstract

The quantification of urea is of the utmost importance not only in medical diagnosis, where it serves as a potential indicator of kidney and liver disfunction, but also in food safety and environmental control. Here, we describe a urea biosensor based on urease entrapped in a crosslinked gelatin hydrogel, deposited onto a fully printed PEDOT:PSS-based organic electrochemical transistor (OECT). The device response is based on the modulation of the channel conductivity by the ionic species produced upon urea hydrolysis catalyzed by the entrapped urease. The biosensor shows excellent reproducibility, a limit of detection as low as 1 μM and a response time of a few minutes. The fabrication of the OECTs by screen-printing on flexible substrates ensures a significant reduction in manufacturing time and costs. The low dimensionality and operational voltages (0.5 V or below) of these devices contribute to make these enzymatic OECT-based biosensors as appealing candidates for high-throughput monitoring of urea levels at the point-of-care or in the field.

2017 - Label-free detection of interleukin-6 using electrolyte gated organic field effect transistors [Articolo su rivista]
Diacci, Chiara; Berto, Marcello; Di Lauro, Michele; Bianchini, Elena; Pinti, Marcello; Simon, Daniel T.; Biscarini, Fabio; Bortolotti, Carlo A.
abstract

Cytokines are small proteins that play fundamental roles in inflammatory processes in the human body. In particular, interleukin (IL)-6 is a multifunctional cytokine, whose increased levels are associated with infection, cancer, and inflammation. The quantification of IL-6 is therefore of primary importance in early stages of inflammation and in chronic diseases, but standard techniques are expensive, time-consuming, and usually rely on fluorescent or radioactive labels. Organic electronic devices and, in particular, organic field-effect transistors (OFETs) have been proposed in the recent years as novel platforms for label-free protein detection, exploiting as sensing unit surface-immobilized antibodies or aptamers. Here, the authors report two electrolyte-gated OFETs biosensors for IL-6 detection, featuring monoclonal antibodies and peptide aptamers adsorbed at the gate. Both strategies yield biosensors that can work on a wide range of IL-6 concentrations and exhibit a remarkable limit of detection of 1 pM. Eventually, electrolyte gated OFETs responses have been used to extract and compare the binding thermodynamics between the sensing moiety, immobilized at the gate electrode, and IL-6.

2017 - Liquid-Gated Organic Electronic Devices Based on High-Performance Solution-Processed Molecular Semiconductor [Articolo su rivista]
DI LAURO, Michele; Berto, Marcello; Giordani, Martina; Benaglia, Simone; Schweicher, Guillaume; Vuillaume, Dominique; Bortolotti, Carlo Augusto; Geerts, Yves H.; Biscarini, Fabio
abstract

High-mobility organic semiconductors such as [1]benzothieno[3,2-b]benzothiophene (BTBT) derivatives are potential candidates for ultrasensitive biosensors. Here 2,7-dioctyl BTBT (C8-BTBT-C8)-based liquid-gated organic electronic devices are demonstrated with two device architectures, viz. electrolyte-gated organic field-effect transistor (EGOFET) and electrolyte-gated organic synapstor (EGOS), and different electrode materials, viz. gold and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS). EGOFETs exhibit a mean transconductance of about 45 µS, on a par with literature, and a max value up to 256 µS at the state-of-the-art in aqueous electrolyte, with a mean product of charge mobility and effective capacitance of about 0.112 and 0.044 µS V−1 for gold and PEDOT:PSS electrodes, respectively. EGOSs exhibit a dynamic response with 15 ms characteristic timescale with Au electrodes and about twice with PEDOT:PSS electrodes. These results demonstrate a promising route for sensing applications in physiological environment based on fully solution-processed whole-organic electronic devices featuring ultrahigh sensitivity and fast response.

2017 - Specific Dopamine Sensing Based on Short-Term Plasticity Behavior of a Whole Organic Artificial Synapse [Articolo su rivista]
Giordani, Martina; Berto, Marcello; Di Lauro, Michele; Bortolotti, Carlo A.; Zoli, Michele; Biscarini, Fabio
abstract

In this work, we demonstrate the ultrasensitive and selective detection of dopamine by means of a neuro-inspired device platform without the need of a specific recognition moiety. The sensor is a whole organic device featuring two electrodes made of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate - PEDOT:PSS - patterned on a polydymethylsiloxane - PDMS - flexible substrate. One electrode is pulsed with a train of voltage square waves, to mimic the presynaptic neuron behavior, while the other is used to record the displacement current, mimicking the postsynaptic neuron. The current response exhibits the features of synaptic Short-Term Plasticity (STP) with facilitating or depressing response according to the stimulus frequency. We found that the response characteristic time USTPdepends on dopamine (DA) concentration in solution. The dose curve exhibits superexponential sensitivity at the lowest concentrations below 1 nM. The sensor detects [DA] down to 1 pM range. We assess the sensor also in the presence of ascorbic acid (AA) and uric acid (UA). Our sensor does not respond to UA, but responds to AA only at concentration above 100 μM. However, it is still able to detect DA down to 1 pM range in the presence of [AA] = 100 μM and 100 pM in the presence of [UA] = 3 μM, these values for AA and UA being the physiological levels in the cerebrospinal fluid and the striatum, respectively.

2016 - Biorecognition in Organic Field Effect Transistors Biosensors: The Role of the Density of States of the Organic Semiconductor [Articolo su rivista]
Berto, Marcello; Casalini, Stefano; Di Lauro, Michele; Marasso, Simone L; Cocuzza, Matteo; Perrone, Denis; Pinti, Marcello; Cossarizza, Andrea; Pirri, Candido F; Simon, Daniel T; Berggren, Magnus; Zerbetto, Francesco; Bortolotti, Carlo Augusto; Biscarini, Fabio
abstract

Biorecognition is a central event in biological processes in the living systems that is also widely exploited in technological and health applications. We demonstrate that the Electrolyte Gated Organic Field Effect Transistor (EGOFET) is an ultrasensitive and specific device that allows us to quantitatively assess the thermodynamics of biomolecular recognition between a human antibody and its antigen, namely, the inflammatory cytokine TNFα at the solid/liquid interface. The EGOFET biosensor exhibits a superexponential response at TNFα concentration below 1 nM with a minimum detection level of 100 pM. The sensitivity of the device depends on the analyte concentration, reaching a maximum in the range of clinically relevant TNFα concentrations when the EGOFET is operated in the subthreshold regime. At concentrations greater than 1 nM the response scales linearly with the concentration. The sensitivity and the dynamic range are both modulated by the gate voltage. These results are explained by establishing the correlation between the sensitivity and the density of states (DOS) of the organic semiconductor. Then, the superexponential response arises from the energy-dependence of the tail of the DOS of the HOMO level. From the gate voltage-dependent response, we extract the binding constant, as well as the changes of the surface charge and the effective capacitance accompanying biorecognition at the electrode surface. Finally, we demonstrate the detection of TNFα in human-plasma derived samples as an example for point-of-care application.

2016 - The substrate is a pH-controlled second gate of electrolyte-gated organic field-effect transistor [Articolo su rivista]
Di Lauro, Michele; Casalini, Stefano; Berto, Marcello; Campana, Alessandra; Cramer, Tobias; Murgia, Mauro; Geoghegan, Mark Anthony; Bortolotti, Carlo Augusto; Biscarini, Fabio
abstract

Electrolyte-gated organic field-effect transistors (EGOFETs), based on ultrathin pentacene films on quartz, were operated with electrolyte solutions whose pH was systematically changed. Transistor parameters exhibit nonmonotonic variation versus pH, which cannot be accounted for by capacitive coupling through the Debye-Helmholtz layer. The data were fitted with an analytical model of the accumulated charge in the EGOFET, where Langmuir adsorption was introduced to describe the pH-dependent charge buildup at the quartz surface. The model provides an excellent fit to the threshold voltage and transfer characteristics as a function of the pH, which demonstrates that quartz acts as a second gate controlled by pH and is mostly effective from neutral to alkaline pH. The effective capacitance of the device is always greater than the capacitance of the electrolyte, thus highlighting the role of the substrate as an important active element for amplification of the transistor response.

2016 - Whole organic electronic synapses for dopamine detection [Relazione in Atti di Convegno]
Giordani, Martina; DI LAURO, Michele; Berto, Marcello; Bortolotti, Carlo Augusto; Vuillaume, Dominique; Gomes, Henrique L.; Zoli, Michele; Biscarini, Fabio
abstract

A whole organic artificial synapse has been fabricated by patterning PEDOT:PSS electrodes on PDMS that are biased in frequency to yield a STP response. The timescale of the STP response is shown to be sensitive to the concentration of dopamine, DA, a neurotransmitter relevant for monitoring the development of Parkinson's disease and potential locoregional therapies. The sensitivity of the sensor towards DA has been validated comparing signal variation in the presence of DA and its principal interfering agent, ascorbic acid, AA. The whole organic synapse is biocompatible, soft and flexible, and is attractive for implantable devices aimed to real-time monitoring of DA concentration in bodily fluids. This may open applications in chronic neurodegenerative diseases such as Parkinson's disease.

2015 - Electrowetting of nitro-functionalized oligoarylene thiols self-assembled on polycrystalline gold [Articolo su rivista]
Casalini, Stefano; Berto, Marcello; Bortolotti, Carlo Augusto; Foschi, Giulia; Operamolla, Alessandra; DI LAURO, Michele; Omar, Omar Hassan; Liscio, Andrea; Pasquali, Luca; Montecchi, Monica; Farinola, Gianluca M; Borsari, Marco
abstract

Four linear terarylene molecules (i) 4-nitro-terphenyl-4″-methanethiol (NTM), (ii) 4-nitro-terphenyl-3″,5″-dimethanethiol (NTD), (iii) ([1,1';4',1″] terphenyl-3,5-diyl)methanethiol (TM), and (iv) ([1,1';4',1″] terphenyl-3,5-diyl)dimethanethiol (TD) have been synthesized and their self-assembled monolayers (SAMs) have been obtained on polycrystalline gold. NTM and NTD SAMs have been characterized by X-ray photoelectron spectroscopy, Kelvin probe measurements, electrochemistry, and contact angle measurements. The terminal nitro group (-NO2) is irreversibly reduced to hydroxylamine (-NHOH), which can be reversibly turned into nitroso group (-NO). The direct comparison between NTM/NTD and TM/TD SAMs unambiguously shows the crucial influence of the nitro group on electrowetting properties of polycrystalline Au. The higher grade of surface tension related to NHOH has been successfully exploited for basic operations of digital μ-fluidics, such as droplets motion and merging.

2015 - Elettronica organica [Voce in Dizionario o Enciclopedia]
Biscarini, Fabio; Berto, Marcello; Campana, Alessandra; DI LAURO, Michele
abstract

Lemma "Elettronica Organica" definisce il settore tecnologico e scientifico, ne descrive i fondamenti e le applicazioni sul mercato e in via di sviluppo.

2015 - Solvent tunes the peroxidase activity of cytochrome c immobilized on kaolinite [Articolo su rivista]
Castellini, Elena; Bernini, Fabrizio; Berto, Marcello; Borsari, Marco; Sola, Marco; Ranieri, Antonio
abstract

The adsorption process and the peroxidase activity of yeast cytochrome c (ycc) immobilized on kaolinite (Kaol) were investigated in mixed ethanol/water solutions. The protein strongly adsorbs on the surface of the clay mineral and the thermodynamic adsorption constant increases with increasing ethanol concentration. The adsorption parameters suggest that in ycc a conformational transition from molten globule to helical state occurs in solution for ethanol concentration above 20%. The peroxidase activity of ycc immobilized on Kaol increases from 0% to 20% ethanol (v/v), then it progressively decreases and almost vanishes in pure ethanol. The catalytic properties of adsorbed yccwere studied in 20 and 40% ethanol solutionswhich correspond to the molten globule and to the helical state, respectively. In both cases, catalysis adheres to theMichaelis–Menten model. Themolten globule state, which binds more weakly to kaolinite than the helical state, was found to be more catalytically active. This study is meant to identify the physicochemical factors that modulate the catalytic activity of this kaolinite-based interface of broad applicability.

2015 - Surface Immobilized His-tagged Azurin as a Model Interface for the Investigation of Vectorial Electron Transfer in Biological Systems [Articolo su rivista]
Casalini, Stefano; Berto, Marcello; Kovtun, Alessandro; Operamolla, Alessandra; DI ROCCO, Giulia; Facci, Paolo; Liscio, Andrea; Farinola, Gianluca M.; Borsari, Marco; Bortolotti, Carlo Augusto
abstract

A model system for the electrochemical investigation of vectorial electron transfer in biological systems was designed, assembled and characterized. Gold electrodes, functionalized with a -OCH3 terminated, aromatic self-assembled monolayer, were used as a substrate for the adsorption of variants of copper- containing, redox metalloprotein azurin. The engineered azurin bears a polyhistidine tag at its C-terminus. Thanks to the presence of the solvent exposed tag, which chelates Cu2+ ions in solution, we introduced an exogenous redox centre. The different reduction potentials of the two redox centres and their positioning with respect to the surface are such that electron transfer from the exogenous copper centre and the electrode is mediated by the native azurin active site, closely paralleling electron transfer processes in naturally occurring multicentre metalloproteins

2013 - Self-Assembly of Mono- And Bidentate Oligoarylene Thiols onto Polycrystalline Au [Articolo su rivista]
Casalini, S.; Berto, M.; Leonardi, F.; Operamolla, A.; Bortolotti, Carlo Augusto; Borsari, Marco; Sun, W.; DI FELICE, Rosa; Corni, Stefano; Albonetti, C.; Hassan Omar, O.; Farinola, G. M.; Biscarini, Fabio
abstract

Four thiolated oligoarylene molecules (i) 4-methoxy-terphenyl-4″-methanethiol (MTM), (ii) 4-methoxy-terphenyl-3″,5″-dimethanethiol (MTD), (iii) 4-nitro-terphenyl-4″-methanethiol (NTM), and (iv) 4-nitro-terphenyl-3″,5″-dimethanethiol (NTD) were synthesized and self-assembled as monolayers (SAMs) on polycrystalline Au electrodes of organic field-effect transistors (OFETs). SAMs were characterized by contact angle and AC/DC electrochemical measurements, whereas atomic force microscopy was used for imaging the pentacene films grown on the coated electrodes. The electrical properties of functionalized OFETs, the electrochemical SAMs features and the morphology of pentacene films were correlated to the molecular organization of the thiolated oligoarylenes on Au, as calculated by means of the density functional theory. This multi-methodological approach allows us to associate the systematic replacement of the SAM anchoring head group (viz. methanethiol and dimethanethiol) and/or terminal tail group (viz. nitro-, -NO2, and methoxy, -OCH3) with the change of the electrical features. The dimethanethiol head group endows SAMs with higher resistive features along with higher surface tensions compared with methanethiol. Furthermore, the different number of thiolated heads affects the kinetics of Au passivation as well as the pentacene morphology. On the other hand, the nitro group confers further distinctive properties, such as the positive shift of both threshold and critical voltages of OFETs with respect to the methoxy one. The latter experimental evidence arise from its electron-withdrawing capability, which has been verified by both DFT calculations and DC electrochemical measurements.