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.

Two Dimensional Heterostructures for Optoelectronics: Current Status and Future Perspective.

Researchers have found various families of two-dimensional (2D) materials and associated heterostructures through detailed theoretical work and experimental efforts. Such primitive studies provide a framework to investigate novel physical/chemical characteristics and technological aspects from micro to nano and pico scale. Two-dimensional van der Waals (vdW) materials and their heterostructures can be obtained to enable high-frequency broadband through a sophisticated combination of stacking order, orientation, and interlayer interactions. These heterostructures have been the focus of much recent research due to their potential applications in optoelectronics. Growing the layers of one kind of 2D material over the other, controlling absorption spectra via external bias, and external doping proposes an additional degree of freedom to modulate the properties of such materials. This mini review focuses on current state-of-the-art material design, manufacturing techniques, and strategies to design novel heterostructures. In addition to a discussion of fabrication techniques, it includes a comprehensive analysis of the electrical and optical properties of vdW heterostructures (vdWHs), particularly emphasizing the energy-band alignment. In the following sections, we discuss specific optoelectronic devices, such as light-emitting diodes (LEDs), photovoltaics, acoustic cavities, and biomedical photodetectors. Furthermore, this also includes a discussion of four different 2D-based photodetector configurations according to their stacking order. Moreover, we discuss the challenges that remain to be addressed in order to realize the full potential of these materials for optoelectronics applications. Finally, as future perspectives, we present some key directions and express our subjective assessment of upcoming trends in the field.

Molecular Doping of CVD-Graphene Surfaces by Perfluoroalkyl-Substituted Perylene Diimides Derivatives.

Non-covalent π-π and dipolar interactions with small aromatic molecules have been widely demonstrated to be a valid option to tune graphene work functions without adding extrinsic scattering centers for charge carriers. In this work, we investigated the interaction between a CVD-graphene monolayer and a thermally evaporated sub-monolayer and the following few-layer thin films of similar perylene diimide derivatives: PDI8-CN2 and PDIF-CN2. The molecular influence on the graphene work function was estimated by XPS and UPS analysis and by investigating the surface potentials via scanning Kelvin probe force microscopy. The perfluorinated decoration and the steric interaction in the early stages of the film growth determined a positive work function shift as high as 0.7 eV in the case of PDIF-CN2, with respect to the value of 4.41 eV for the intrinsic graphene. Our results unambiguously highlight the absence of valence band shifts in the UPS analysis, indicating the prevalence of dipolar interactions between the graphene surface and the organic species enhanced by the presence of the fluorine-enriched moieties.

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.

Microconfined flow behavior of red blood cells.

Red blood cells (RBCs) perform essential functions in human body, such as gas exchange between blood and tissues, thanks to their ability to deform and flow in the microvascular network. The high RBC deformability is mainly due to the viscoelastic properties of the cell membrane. Since an impaired RBC deformability could be found in some diseases, such as malaria, sickle cell anemia, diabetes and hereditary disorders, there is the need to provide further insight into measurement of RBC deformability in a physiologically relevant flow field. Here, RBCs deformability has been studied in terms of the minimum apparent plasma-layer thickness by using high-speed video microscopy of RBCs flowing in cylindrical glass capillaries. An in vitro systematic microfluidic investigation of RBCs in micro-confined conditions has been performed, resulting in the determination of the RBCs time recovery constant, RBC volume and surface area and RBC membrane shear elastic modulus and surface viscosity. It has been noticed that the deformability of RBCs induces cells aggregation during flow in microcapillaries, allowing the formation of clusters of cells. Overall, our results provide a novel technique to estimate RBC deformability and also RBCs collective behavior, which can be used for the analysis of pathological RBCs, for which reliable quantitative methods are still lacking.

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.

Chemisorption, morphology, and structure of a n-type perylene diimide derivative at the interface with gold: influence on devices from thin films to single molecules.

We have investigated thin films of a perylene diimide derivative with a cyano-functionalized core (PDI-8CN2) deposited on Au(111) single crystals from the monolayer to the multilayer regime. We found that PDI-8CN2 is chemisorbed on gold. The molecules experience a thickness-dependent reorientation, and a 2D growth mode with molecular stepped terraces is achieved adopting low deposition rates. The obtained results are discussed in terms of their impact on field effect devices, also clarifying why the use of substrate/contact treatments, decoupling PDI-8CN2 molecules from the substrate/contacts, is beneficial for such devices. Our results also suggest that perylene diimide derivatives with CN bay-functionalization are very promising candidates for single-molecule electronic devices.

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.

Structural, electronic and vibrational properties of N,N'-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDI-FCN2) crystal.

We present a theoretical and experimental investigation of the crystalline structure of N,N'-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDI-FCN2) that has been deduced combining experimental XRD data, obtained from powders, with global-optimization algorithms which allow to identify Bravais lattice, primitive cell parameters, and space group of the crystal. The XRD spectrum calculated for the proposed crystalline structure very well reproduces the measured XRD data. Our results suggest the triclinic lattice structure of spatial groups P1 and P1, respectively, for the crystalline PDI-FCN2-1,7 and PDI-FCN2-1,6 isomers. In both cases, the primitive cell contains a single molecule. On the proposed crystalline structures, KS-DFT cell energy calculations, including van der Waals interactions, have been performed to assign the minimum energy geometrical structure and orientation of the molecule inside the corresponding primitive cell. These calculations evidence the molecular packing that characterizes the strong anisotropy of the PDI-FCN2 crystal. Electronic band-structures calculated for both isomers within the Kohn-Sham density-functional theory indicate that the crystalline P1 structure is an indirect gap semiconductor, while the P1 structure is a direct gap semiconductor. The electronic band structure calculations on the optimized crystal geometries highlight strong anisotropy in the dispersion curves E(k), which roots at the molecular packing in the crystal. Finally, the vibrational spectrum of both crystalline isomers has been calculated in the harmonic approximation and the dominant vibrational frequencies have been associated to collective motions of selected atoms in the molecules.

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.