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.

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.

Novel Thienyl DPP derivatives Functionalized with Terminal Electron-Acceptor Groups: Synthesis, Optical Properties and OFET Performance.

Three novel diketopyrrolopyrrole (DPP) based small molecules have been synthesized and characterized in terms of their chemical-physical, electrochemical and electrical properties. All the molecules consist of a central DPP electron acceptor core symmetrically functionalized with donor bi-thienyl moieties and flanked in the terminal positions by three different auxiliary electron-acceptor groups. This kind of molecular structure, characterized by an alternation of electron acceptor and donor groups, was purposely designed to provide a significant absorption at the longer wavelengths of the visible spectrum: when analysed as thin films, in fact, the dyes absorb well over 800 nm and exhibit a narrow optical bandgap down to 1.28 eV. A detailed DFT analysis provides useful information on the electronic structure of the dyes and on the features of the main optical transitions. Organic field-effect transistors (OFETs) have been fabricated by depositing the DPP dyes as active layers from solution: the different end-functionalization of the dyes had an effect on the charge-transport properties with two of the dyes acting as n-type semiconductors (electron mobility up to 4.4 ⋅ 10-2  cm2 /V ⋅ s) and the third one as a p-type semiconductor (hole mobility up to 2.3 ⋅ 10-3  cm2 /V ⋅ s). Interestingly, well-balanced ambipolar transistors were achieved by blending the most performant n-type and p-type dyes with hole and electron mobility in the order of 10-3  cm2 /V ⋅ s.

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.

Balanced Ambipolar Charge Transport in Phenacene/Perylene Heterojunction-Based Organic Field-Effect Transistors.

Electronic devices relying on the combination of different conjugated organic materials are considerably appealing for their potential use in many applications such as photovoltaics, light emission, and digital/analog circuitry. In this study, the electrical response of field-effect transistors achieved through the evaporation of picene and PDIF-CN2 molecules, two well-known organic semiconductors with remarkable charge transport properties, was investigated. With the main goal to get a balanced ambipolar response, various device configurations bearing double-layer, triple-layer, and codeposited active channels were analyzed. The most suitable choices for the layer deposition processes, the related characteristic parameters, and the electrode position were identified to this purpose. In this way, ambipolar organic field-effect transistors exhibiting balanced mobility values exceeding 0.1 cm2 V-1 s-1 for both electrons and holes were obtained. These experimental results highlight also how the combination between picene and PDIF-CN2 layers allows tuning the threshold voltages of the p-type response. Scanning Kelvin probe microscopy (SKPM) images acquired on picene/PDIF-CN2 heterojunctions suggest the presence of an interface dipole between the two organic layers. This feature is related to the partial accumulation of space charge at the interface being enhanced when the electrons are depleted in the underlayer.

Post-Deposition Wetting and Instabilities in Organic Thin Films by Supersonic Molecular Beam Deposition.

We discuss the formation and post-deposition instability of nanodrop-like structures in thin films of PDIF-CN2 (a perylene derivative) deposited via supersonic molecular beam deposition technique on highly hydrophobic substrates at room temperature. The role of the deposition rate on the characteristic lengths of the organic nanodrops has been investigated by a systematic analysis of atomic force microscope images of the thin films and through the use of the height-height correlation function. The nanodrops appear to be a metastable configuration for the freshly-deposited films. For this reason, post-deposition wetting effect has been examined with unprecedented accuracy throughout a year of experimental observations. The observed time scales, from few hours to months, are related to the growth rate, and characterize the thin films morphological reordering from three-dimensional nanodrops to a well-connected terraced film. While the interplay between adhesion and cohesion energies favors the formation of 3D-mounted structures during the growth, wetting phenomenon following the switching off of the molecular flux is found to be driven by an instability. A slow rate downhill process survives at the molecular flux shutdown and it is accompanied and maybe favored by the formation of a precursor layer composed of more lying molecules. These results are supported by simulations based on a non-linear stochastic model. The instability has been simulated, for both the growth and the post-growth evolution. To better reproduce the experimental data it is needed to introduce a surface equalizer term characterized by a relaxation time taking into account the presence of a local mechanism of molecular correlation.

Subnanometer Resolution and Enhanced Friction Contrast at the Surface of Perylene Diimide PDI8-CN2 Thin Films in Ambient Conditions.

We report high-resolution surface morphology and friction force maps of polycrystalline organic thin films derived by deposition of the n-type perylene diimide semiconductor PDI8-CN2. We show that the in-plane molecular arrangement into ordered, cofacial slip-stacked rows results in a largely anisotropic surface structure, with a characteristic sawtooth corrugation of a few Ångstroms wavelength and height. Load-controlled experiments reveal different types of friction contrast between the alternating sloped and stepped regions, with transitions from atomic-scale dissipative stick-slip to smooth sliding with ultralow friction within the surface unit cell. Notably, such a rich phenomenology is captured under ambient conditions. We demonstrate that friction contrast is well reproduced by numerical simulations assuming a reduced corrugation of the tip-molecule potential nearby the step edges. We propose that the side alkyl chains pack into a compact low-surface-energy overlayer, and friction modulation reflects periodic heterogeneity of chains bending properties and subsurface anchoring to the perylene cores.

Single-Molecule Break Junctions Based on a Perylene-Diimide Cyano-Functionalized (PDI8-CN2) Derivative.

In this letter, we report the single-molecule conductance properties of a cyano-functionalized perylene-diimide derivative (PDI8-CN2) investigated with gold nano-electrodes. This molecule is of large interest for the fabrication of high-performance and air-stable n-type organic field-effect transistors. Low-bias experiments performed on mechanically controllable break junctions reveal the presence of two different values of the single-molecule conductance, which differ by about two orders of magnitudes. Up to date, this feature was never observed for other perylene-diimide compounds having alternative chemical moieties attached to the basic aromatic core. Theoretical calculations suggest that the highest single-molecule conductance value here observed, comprised between 10(-2) and 10(-3) G0, is related to a charge transport path directly linking the two cyano groups.

Hybrid organic-inorganic porous semiconductor transducer for multi-parameters sensing.

Porous silicon (PSi) non-symmetric multi-layers are modified by organic molecular beam deposition of an organic semiconductor, namely the N,N'-1H,1H-perfluorobutyldicyanoperylene-carboxydi-imide (PDIF-CN2). Joule evaporation of PDIF-CN2 into the PSi sponge-like matrix not only improves but also adds transducing skills, making this solid-state device a dual signal sensor for chemical monitoring. PDIF-CN2 modified PSi optical microcavities show an increase of about five orders of magnitude in electric current with respect to the same bare device. This feature can be used to sense volatile substances. PDIF-CN2 also improves chemical resistance of PSi against alkaline and acid corrosion.

Melanin-Inspired Organic Electronics: Electroluminescence in Asymmetric Triazatruxenes.

The oxidative polymerization of 5,6-dihydroxyindoles and related hydroxyindoles at pH<3 is diverted from the usual eumelanin-forming pathway to produce mixtures of symmetric and asymmetric triazatruxenes (TATs), which could be separated and characterized for their opto-electronic properties with the aid of TD-DFT calculations. Data showed that the asymmetric isomers exhibit higher fluorescence quantum efficiencies, lower HOMO-LUMO gaps, better film homogeneity, and a more definite aggregation behavior than the symmetric counterparts, suggesting promising applications in organic electronics. The enhanced luminance exhibited by the OLED devices fabricated with blends of the synthesized TATs in poly-9-vinylcarbazole confirmed the potential of the asymmetric skeleton as new versatile platform for light-emitting materials.

Melanin-Inspired Organic Electronics: Electroluminescence in Asymmetric Triazatruxenes.

Invited for this month's cover is the group of Dr. Paola Manini from the University of Naples Federico II. The cover picture shows the concept underlying the design of a melanin-inspired electroluminescent material for OLED devices. This article is part of a well-structured research project aimed at imitating Nature's most enigmatic and fascinating functional pigments for the design and synthesis of innovative biomaterials for organic electronics applications. Read the full text of the article at 10.1002/cplu.201402444.

Cardiomyocyte differentiation of embryonic stem cells on the surface of organic semiconductors.

PURPOSE: Electrically active supports provide new horizons for bio-sensing and artificial organ design. Cell-based electrochemical biosensors can be used as bio-microactuators, applied to the biorobotics. Microchip-based bioassay systems can provide real-time cell analysis for preclinical drug design or for intelligent drug delivery devices. In regenerative medicine, electrically active supports can be used as bio-reactors to monitor cell activity, optimize the stem cell differentiation and control cell and tissue morphology. Biocompatibility and direct interaction of the electrically active surface with the cell surface is a critical aspect of this technology.
 METHODS: In this work embryonic stem cells (AK7 ES) have been cultivated on the surface of thin films achieved through the evaporation of two aromatic compounds (T6 and PDI-8CN2 ) of particular interest for the fabrication of organic field-effect transistors (OFET). One of the potential advantages offered by the application of OFETs as bio-electronic supports is that they represent a powerful tool for the detection of bio-signals because their electrically active surface is an organic film.
 RESULTS: The cell morphology on T6 and PDI-8CN2 surface shows to be similar to the usual cell appearance, as obtained when standard culture support (petri dish) are employed. Moreover, our experimental results demonstrate that stem cells can be lead to differentiation up to "beating" cardiomyocytes even on these electrically-active organic films.
 CONCLUSIONS: This investigation encourages the perspective to develop OFET-based biosensors in order to accurately characterize stem cells during the cardiac differentiation process and eventually increase their differentiation efficiency.

Microfluidics analysis of red blood cell membrane viscoelasticity.

In this work, a microfluidic system to investigate the flow behavior of red blood cells in a microcirculation-mimicking network of PDMS microchannels with thickness comparable to cell size is presented. We provide the first quantitative description of cell velocity and shape as a function of the applied pressure drop in such devices. Based on these results, a novel methodology to measure cell membrane viscoelastic properties in converging/diverging flow is developed, and the results are in good agreement with data from the literature. In particular, in the diverging channel the effect of RBC surface viscosity is dominant with respect to shear elasticity. Possible applications include measurements of cell deformability in pathological samples, where reliable methods are still lacking.