High versatility of polyethylene terephthalate (PET) waste for the development of batteries, biosensing and gas sensing devices.

Continuously growing adoption of electronic devices in energy storage, human health and environmental monitoring systems increases demand for cost-effective, lightweight, comfortable, and highly efficient functional structures. In this regard, the recycling and reuse of polyethylene terephthalate (PET) waste in the aforementioned fields due to its excellent mechanical properties and chemical resistance is an effective solution to reduce plastic waste. Herein, we review recent advances in synthesis procedures and research studies on the integration of PET into energy storage (Li-ion batteries) and the detection of gaseous and biological species. The operating principles of such systems are described and the role of recycled PET for various types of architectures is discussed. Modifying the composition, crystallinity, surface porosity, and polar surface functional groups of PET are important factors for tuning its features as the active or substrate material in biological and gas sensors. The findings indicate that conceptually new pathways to the study are opened up for the effective application of recycled PET in the design of Li-ion batteries, as well as biochemical and catalytic detection systems. The current challenges in these fields are also presented with perspectives on the opportunities that may enable a circular economy in PET use.

Silk Fibroin Materials: Biomedical Applications and Perspectives.

The golden rule in tissue engineering is the creation of a synthetic device that simulates the native tissue, thus leading to the proper restoration of its anatomical and functional integrity, avoiding the limitations related to approaches based on autografts and allografts. The emergence of synthetic biocompatible materials has led to the production of innovative scaffolds that, if combined with cells and/or bioactive molecules, can improve tissue regeneration. In the last decade, silk fibroin (SF) has gained attention as a promising biomaterial in regenerative medicine due to its enhanced bio/cytocompatibility, chemical stability, and mechanical properties. Moreover, the possibility to produce advanced medical tools such as films, fibers, hydrogels, 3D porous scaffolds, non-woven scaffolds, particles or composite materials from a raw aqueous solution emphasizes the versatility of SF. Such devices are capable of meeting the most diverse tissue needs; hence, they represent an innovative clinical solution for the treatment of bone/cartilage, the cardiovascular system, neural, skin, and pancreatic tissue regeneration, as well as for many other biomedical applications. The present narrative review encompasses topics such as (i) the most interesting features of SF-based biomaterials, bare SF's biological nature and structural features, and comprehending the related chemo-physical properties and techniques used to produce the desired formulations of SF; (ii) the different applications of SF-based biomaterials and their related composite structures, discussing their biocompatibility and effectiveness in the medical field. Particularly, applications in regenerative medicine are also analyzed herein to highlight the different therapeutic strategies applied to various body sectors.

Organic Electrochemical Transistor Immuno-Sensors for Spike Protein Early Detection.

The global COVID-19 pandemic has had severe consequences from the social and economic perspectives, compelling the scientific community to focus on the development of effective diagnostics that can combine a fast response and accurate sensitivity/specificity performance. Presently available commercial antigen-detecting rapid diagnostic tests (Ag-RDTs) are very fast, but still face significant criticisms, mainly related to their inability to amplify the protein signal. This translates to a limited sensitive outcome and, hence, a reduced ability to hamper the spread of SARS-CoV-2 infection. To answer the urgent need for novel platforms for the early, specific and highly sensitive detection of the virus, this paper deals with the use of organic electrochemical transistors (OECTs) as very efficient ion-electron converters and amplifiers for the detection of spike proteins and their femtomolar concentration. The electrical response of the investigated OECTs was carefully analyzed, and the changes in the parameters associated with the transconductance (i.e., the slope of the transfer curves) in the gate voltage range between 0 and 0.3 V were found to be more clearly correlated with the spike protein concentration. Moreover, the functionalization of OECT-based biosensors with anti-spike and anti-nucleocapside proteins, the major proteins involved in the disease, demonstrated the specificity of these devices, whose potentialities should also be considered in light of the recent upsurge of the so-called "long COVID" syndrome.

Kombucha electronics: electronic circuits on kombucha mats.

A kombucha is a tea and sugar fermented by over sixty kinds of yeasts and bacteria. This symbiotic community produces kombucha mats, which are cellulose-based hydrogels. The kombucha mats can be used as an alternative to animal leather in industry and fashion once they have been dried and cured. Prior to this study, we demonstrated that living kombucha mats display dynamic electrical activity and distinct stimulating responses. For use in organic textiles, cured mats of kombucha are inert. To make kombucha wearables functional, it is necessary to incorporate electrical circuits. We demonstrate that creating electrical conductors on kombucha mats is possible. After repeated bending and stretching, the circuits maintain their functionality. In addition, the abilities and electronic properties of the proposed kombucha, such as being lighter, less expensive, and more flexible than conventional electronic systems, pave the way for their use in a diverse range of applications.

Immuno-Sensing at Ultra-Low Concentration of TG2 Protein by Organic Electrochemical Transistors.

Transglutaminase 2 (TG2) is a ubiquitously expressed member of the transglutaminase family with Ca2+-dependent protein crosslinking activity. Its subcellular localization is crucial in determining its function, and indeed, TG2 is found in the extracellular matrix, mitochondria, recycling endosomes, plasma membrane, cytosol, and nucleus because it is associated with cell growth, differentiation, and apoptosis. It is involved in several pathologies, such as celiac disease, cardiovascular, hepatic, renal, and fibrosis diseases, carrying out opposite functions of up and down regulation in the progression of the same pathology. Therefore, this fine regulation requires a very sensitive and specific method of identification of TG2, which is to be detected in very small quantities in a deregulated condition. Here, we demonstrate the possibility of detecting TG2 down to attomolar concentration by using organic electrochemical transistors driven by gold electrodes functionalized with anti-TG2 antibodies. In particular, a direct correlation between the TG2 concentration and the transistor transconductance values, as extracted from typical transfer curves, was found. Overall, our findings highlight the potentialities of this new biosensing approach for the detection of TG2 in the context of pathological diseases, offering a rapid and cost-effective alternative to traditional methods.

Lab on a Chip Device for Diagnostic Evaluation and Management in Chronic Renal Disease: A Change Promoting Approach in the Patients' Follow Up.

Lab-on-a-chip (LOC) systems are miniaturized devices aimed to perform one or several analyses, normally carried out in a laboratory setting, on a single chip. LOC systems have a wide application range, including diagnosis and clinical biochemistry. In a clinical setting, LOC systems can be associated with the Point-of-Care Testing (POCT) definition. POCT circumvents several steps in central laboratory testing, including specimen transportation and processing, resulting in a faster turnaround time. Provider access to rapid test results allows for prompt medical decision making, which can lead to improved patient outcomes, operational efficiencies, patient satisfaction, and even cost savings. These features are particularly attractive for healthcare settings dealing with complicated patients, such as those affected by chronic kidney disease (CKD). CKD is a pathological condition characterized by progressive and irreversible structural or functional kidney impairment lasting for more than three months. The disease displays an unavoidable tendency to progress to End Stage Renal Disease (ESRD), thus requiring renal replacement therapy, usually dialysis, and transplant. Cardiovascular disease (CVD) is the major cause of death in CKD, with a cardiovascular risk ten times higher in these patients than the rate observed in healthy subjects. The gradual decline of the kidney leads to the accumulation of uremic solutes, with negative effect on organs, especially on the cardiovascular system. The possibility to monitor CKD patients by using non-invasive and low-cost approaches could give advantages both to the patient outcome and sanitary costs. Despite their numerous advantages, POCT application in CKD management is not very common, even if a number of devices aimed at monitoring the CKD have been demonstrated worldwide at the lab scale by basic studies (low Technology Readiness Level, TRL). The reasons are related to both technological and clinical aspects. In this review, the main technologies for the design of LOCs are reported, as well as the available POCT devices for CKD monitoring, with a special focus on the most recent reliable applications in this field. Moreover, the current challenges in design and applications of LOCs in the clinical setting are briefly discussed.

Organic Bioelectronics Development in Italy: A Review.

In recent years, studies concerning Organic Bioelectronics have had a constant growth due to the interest in disciplines such as medicine, biology and food safety in connecting the digital world with the biological one. Specific interests can be found in organic neuromorphic devices and organic transistor sensors, which are rapidly growing due to their low cost, high sensitivity and biocompatibility. This trend is evident in the literature produced in Italy, which is full of breakthrough papers concerning organic transistors-based sensors and organic neuromorphic devices. Therefore, this review focuses on analyzing the Italian production in this field, its trend and possible future evolutions.

A 17.7µW CDS-CTIA for Wireless-powered Wearable Electrochemical Sweat Sensors.

A capacitor transimpedance amplifier (CTIA) for wireless-powered wearable electrochemical sweat sensors is designed and tested. Correlative double sampling (CDS) technology is utilized to suppress offset voltage and noise. Dedicated low-power and low-voltage designs meet the requirements of wireless-powered wearable applications where the power supply is limited, and voltage is unstable. The proposed CDS-CTIA is fabricated in 0.18-µm complementary metal oxide semiconductor (CMOS) process, occupying an active area of 0.0285mm2. The measured low-frequency gain is 33.2MΩ/150.4dBΩ under a 1.8V supply voltage, with a total power consumption of 17.694µW (including 14.882µW static power and 2.812µW dynamic power). The input current ranges from -24nA to +19nA, and the input referred noise current is 7.76pArms in the 0.1-100 Hz frequency band. The proposed CDS-CTIA is capable of operating under a wide power supply ranging from 0.9V to 2.0V. In addition, its practicality is verified by measuring glucose concentration with an enzyme electrode.

Organic electrochemical transistors as novel biosensing platforms to study the electrical response of whole blood and plasma.

In this paper, for the first time to the best of our knowledge, organic electrochemical transistors are employed to investigate the electrical response of human blood, plasma and alternative buffer solutions that inhibit red blood cell (RBC) aggregation. Our focus is on selecting a suitable electrolytic platform and the related operating conditions, where the RBC effect on the OECT response can be observed separately from the strong ionic environment of plasma in whole blood. The transient response of whole blood to pulse experiments is characterized by two time constants, which can be related to blood viscosity and to the capacitive coupling between the ionic and electronic components of the overall system. The role of capacitive effects, likely due to enhanced double-layer formation by negatively charged RBCs, is also confirmed by the increase of transconductance which was found in RBC suspensions as compared to the suspending buffer. Overall, the complex behavior found in these experiments provides new insights for the development of innovative blood-based sensing devices for biomedical applications.

Homocysteine Solution-Induced Response in Aerosol Jet Printed OECTs by Means of Gold and Platinum Gate Electrodes.

Homocysteine (Hcy) is a non-protein, sulfur-containing amino acid, which is recognized as a possible risk factor for coronary artery and other pathologies when its levels in the blood exceed the normal range of between 5 and 12 µmol/L (hyperhomocysteinemia). At present, standard procedures in laboratory medicine, such as high-performance liquid chromatography (HPLC), are commonly employed for the quantitation of total Hcy (tHcy), i.e., the sum of the protein-bound (oxidized) and free (homocystine plus reduced Hcy) forms, in biological fluids (particularly, serum or plasma). Here, the response of Aerosol Jet-printed organic electrochemical transistors (OECTs), in the presence of either reduced (free) and oxidized Hcy-based solutions, was analyzed. Two different experimental protocols were followed to this end: the former consisting of gold (Au) electrodes' biothiol-induced thiolation, while the latter simply used bare platinum (Pt) electrodes. Electrochemical impedance spectroscopy (EIS) analysis was performed both to validate the gold thiolation protocol and to gain insights into the reduced Hcy sensing mechanism by the Au-gated OECTs, which provided a final limit of detection (LoD) of 80 nM. For the OECT response based on Platinum gate electrodes, on the other hand, a LoD of 180 nM was found in the presence of albumin-bound Hcy, with this being the most abundant oxidized Hcy-form (i.e., the protein-bound form) in physiological fluids. Despite the lack of any biochemical functionalization supporting the response selectivity, the findings discussed in this work highlight the potential role of OECT in the development of low-cost point-of-care (POC) electronic platforms that are suitable for the evaluation, in humans, of Hcy levels within the physiological range and in cases of hyperhomocysteinemia.

Interfacing aptamers, nanoparticles and graphene in a hierarchical structure for highly selective detection of biomolecules in OECT devices.

In several biomedical applications, the detection of biomarkers demands high sensitivity, selectivity and easy-to-use devices. Organic electrochemical transistors (OECTs) represent a promising class of devices combining a minimal invasiveness and good signal transduction. However, OECTs lack of intrinsic selectivity that should be implemented by specific approaches to make them well suitable for biomedical applications. Here, we report on a biosensor in which selectivity and a high sensitivity are achieved by interfacing, in an OECT architecture, a novel gate electrode based on aptamers, Au nanoparticles and graphene hierarchically organized to optimize the final response. The fabricated biosensor performs state of the art limit of detection monitoring biomolecules, such as thrombin-with a limit of detection in the picomolar range (≤ 5 pM) and a very good selectivity even in presence of supraphysiological concentrations of Bovine Serum Albumin (BSA-1mM). These accomplishments are the final result of the gate hierarchic structure that reduces sterich indrance that could contrast the recognition events and minimizes false positive, because of the low affinity of graphene towards the physiological environment. Since our approach can be easily applied to a large variety of different biomarkers, we envisage a relevant potential for a large series of different biomedical applications.

Rapid prototyping of 3D Organic Electrochemical Transistors by composite photocurable resin.

Rapid Prototyping (RP) promises to induce a revolutionary impact on how the objects can be produced and used in industrial manufacturing as well as in everyday life. Over the time a standard technique as the 3D Stereolithography (SL) has become a fundamental technology for RP and Additive Manufacturing (AM), since it enables the fabrication of the 3D objects from a cost-effective photocurable resin. Efforts to obtain devices more complex than just a mere aesthetic simulacre, have been spent with uncertain results. The multidisciplinary nature of such manufacturing technique furtherly hinders the route to the fabrication of complex devices. A good knowledge of the bases of material science and engineering is required to deal with SL technological, characterization and testing aspects. In this framework, our study aims to reveal a new approach to obtain RP of complex devices, namely Organic Electro-Chemical Transistors (OECTs), by SL technique exploiting a resin composite based on the conductive poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and the photo curable Poly(ethylene glycol) diacrylate (PEGDA). A comprehensive study is presented, starting from the optimization of composite resin and characterization of its electrochemical properties, up to the 3D OECTs printing and testing. Relevant performances in biosensing for dopamine (DA) detection using the 3D OECTs are reported and discussed too.

Scaling Organic Electrochemical Transistors Down to Nanosized Channels.

The perspective of downscaling organic electrochemical transistors (OECTs) in the nanorange is approached by depositing poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on electrodes with a nanogap designed and fabricated by electromigration induced break junction (EIBJ) technique. The electrical response of the fabricated devices is obtained by acquiring transfer characteristics in order to clarify the specific main characteristics of OECTs with sub-micrometer-sized active channels (nanogap-OECTs). On the basis of their electrical response to different scan times, the nanogap-OECT shows a maximum transconductance unaffected upon changing scan times in the time window from 1 s to 100 µs, meaning that fast varying signals can be easily acquired with unchanged amplifying performance. Hence, the scaling down of the channel size to the nanometer scale leads to a geometrical paradigm that minimizes effects on device response due to the cationic diffusion into the polymeric channel. A comprehensive study of these features is carried out by an electrochemical impedance spectroscopy (EIS) study, complemented by a quantitative analysis made by equivalent circuits. The propagation of a redox front into the polymer bulk due to ionic diffusion also known as the "intercalation pseudocapacitance" is identified as a limiting factor for the transduction dynamics.

Multifunctional Operation of an Organic Device with Three-Dimensional Architecture.

This work aims to show the feasibility of an innovative approach for the manufacturing of organic-based devices with a true three-dimensional and customizable structure that is made possible by plastic templates, fabricated by additive manufacturing methods, and coated by conducting organic thin films. Specifically, a three-dimensional prototype based on a polyamide structure covered by poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) using the dip-coating technique demonstrated a multifunctional character. The prototype is indeed able to operate both as a three-terminal device showing the typical response of organic electrochemical transistors (OECTs), with a higher amplification performance with respect to planar (2D) all-PEDOT:PSS OECTs, and as a two-terminal device able to efficiently implement a resistive sensing of water vaporization and perspiration, showing performances at least comparable to that of state-of-art resistive humidity sensors based on pristine PEDOT:PSS. To our knowledge, this is the first reported proof-of-concept of a true 3D structured OECT, obtained by exploiting a Selective laser sintering approach that, though simple in terms of 3D layout, paves the way for the integration of sensors based on OECTs into three-dimensional objects in various application areas.

PEDOT:PSS Morphostructure and Ion-To-Electron Transduction and Amplification Mechanisms in Organic Electrochemical Transistors.

Organic electrochemical transistors (OECTs) represent a powerful and versatile type of organic-based device, widely used in biosensing and bioelectronics due to potential advantages in terms of cost, sensitivity, and system integration. The benchmark organic semiconductor they are based on is poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), the electrical properties of which are reported to be strongly dependent on film morphology and structure. In particular, the literature demonstrates that film processing induces morphostructural changes in terms of conformational rearrangements in the PEDOT:PSS in-plane phase segregation and out-of-plane vertical separation between adjacent PEDOT-rich domains. Here, taking into account these indications, we show the thickness-dependent operation of OECTs, contextualizing it in terms of the role played by PEDOT:PSS film thickness in promoting film microstructure tuning upon controlled-atmosphere long-lasting thermal annealing (LTA). To do this, we compared the LTA-OECT response to that of OECTs with comparable channel thicknesses that were exposed to a rapid thermal annealing (RTA). We show that the LTA process on thicker films provided OECTs with an enhanced amplification capability. Conversely, on lower thicknesses, the LTA process induced a higher charge carrier modulation when the device was operated in sensing mode. The provided experimental characterization also shows how to optimize the OECT response by combining the control of the microstructure via solution processing and the effect of postdeposition processing.

Integration of organic electrochemical transistors and immuno-affinity membranes for label-free detection of interleukin-6 in the physiological concentration range through antibody-antigen recognition.

We demonstrate the label-free and selective detection of interleukin-6 (IL-6), a key cell-signaling molecule in biology and medicine, by integrating an OECT with an immuno-affinity regenerated cellulose membrane. The objective of the membrane is to increase the local concentration of IL-6 at the sensing electrode and, thereby, enhance the device response for concentrations falling within the physiological concentration range of cytokines. The OECT gate electrode is functionalized with an oligo(ethylene glycol)-terminated self-assembled alkanethiolate monolayer (SAM) for both the immobilization of anti IL-6 antibodies and the inhibition of non-specific biomolecule binding. The OECT gate/electrolyte interface is exploited for the selective detection of IL-6 through the monitoring of antigen-antibody binding events occurring at the gate electrode.

Drug-induced cellular death dynamics monitored by a highly sensitive organic electrochemical system.

We propose and demonstrate a sensitive diagnostic device based on an Organic Electrochemical Transistor (OECT) for direct in-vitro monitoring cell death. The system efficiently monitors cell death dynamics, being able to detect signals related to specific death mechanisms, namely necrosis or early/late apoptosis, demonstrating a reproducible correlation between the OECT electrical response and the trends of standard cell death assays. The innovative design of the Twell-OECT system has been modeled to better correlate electrical signals with cell death dynamics. To qualify the device, we used a human lung adenocarcinoma cell line (A549) that was cultivated on the micro-porous membrane of a Transwell (Twell) support, and exposed to the anticancer drug doxorubicin. Time-dependent and dose-dependent dynamics of A549 cells exposed to doxorubicin are evaluated by monitoring cell death upon exposure to a range of doses and times that fully covers the protocols used in cancer treatment. The demonstrated ability to directly monitor cell stress and death dynamics upon drug exposure using simple electronic devices and, possibly, achieving selectivity to different cell dynamics is of great interest for several application fields, including toxicology, pharmacology, and therapeutics.

Liposome sensing and monitoring by organic electrochemical transistors integrated in microfluidics.

BACKGROUND: Organic electrochemical transistors (OECTs), which are becoming more and more promising devices for applications in bioelectronics and nanomedicine, are proposed here as ideally suitable for sensing and real time monitoring of liposome-based structures. This is quite relevant since, currently, the techniques used to investigate liposomal structures, their stability in different environments as well as drug loading and delivery mechanisms, operate basically off-line and/or with pre-prepared sampling. METHODS: OECTs, based on the PEDOT:PSS conductive polymer, have been employed as sensors of liposome-based nanoparticles in electrolyte solutions to assess sensitivity and monitoring capabilities based on ion-to-electron amplified transduction. RESULTS: We demonstrate that OECTs are very efficient, reliable and sensitive devices for detecting liposome-based nanoparticles on a wide dynamic range down to 10(-5)mg/ml (with a lowest detection limit, assessed in real-time monitoring, of 10(-7)mg/ml), thus matching the needs of typical drug loading/drug delivery conditions. They are hence particularly well suited for real-time monitoring of liposomes in solution. Furthermore, OECTs are shown to sense and discriminate successive injection of different liposomes, so that they could be good candidates in quality-control assays or in the pharmaceutical industry. GENERAL SIGNIFICANCE: Drug loading and delivery by liposome-based structures is a fast growing and very promising field that will strongly benefit from real-time, highly sensitive and low cost monitoring of their dynamics in different pharma and biomedical environments, with a particular reference to the pharmaceutical and production processes, where a major issue is monitoring and measuring the formation and concentration of liposomes and the relative drug load. The demonstrated ability to sense and monitor complex bio-structures, such as liposomes, paves the way for very promising developments in biosensing and nanomedicine. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine.

Irreversible evolution of eumelanin redox states detected by an organic electrochemical transistor: en route to bioelectronics and biosensing.

Organic electrochemical transistors (OECTs) are currently emerging as powerful tools for biosensing, bioelectronics and nanomedical applications owing to their ability to operate under liquid phase conditions optimally integrating electronic and biological systems. Herein we disclose the unique potential of OECTs for detecting and investigating the electrical properties of insoluble eumelanin biopolymers. Gate current measurements on fine aqueous suspensions of a synthetic eumelanin sample from 5,6-dihydroxyindole (DHI) revealed a well detectable hysteretic response similar to that of the pure monomer in solution, with the formal concentration of the polymer as low as 10-6 M. Induction of the gate current would reflect electron transfer from solid eumelanin to the Pt-electrode sustained by redox active catechol/quinone components of the polymer. A gradual decrease in gate current and areas subtended by hysteretic loops were observed over 5 cycles both in the eumelanin- and DHI-based devices, suggesting evolution of the polymer from a far-from-the-equilibrium redox state toward a more stable electronic arrangement promoted by redox exchange with the gate electrode. OECTs are thus proposed as valuable tools for the efficient heterogeneous-phase sensing of eumelanins and to gauge their peculiar electrical and redox behaviour.