Self-Assembly and Electrical Conductivity of a New [1]benzothieno[3,2-b][1]-benzothiophene (BTBT)-Peptide Hydrogel.

The conjugation of small-molecule semiconductors with self-assembling peptides is a powerful tool for the fabrication of supramolecular soft materials for organic electronics and bioelectronics. Herein, we introduced the benchmark organic semiconductor [1]benzothieno[3,2-b][1]-benzothiophene (BTBT) within the structure of a self-assembling amphipathic peptide. The molecular structure of the conjugate was rationally designed to favour π-π stacking between BTBT cores and π-delocalization within the self-assembled architectures. Hydrogels with fibrillar structure were obtained upon self-assembly. Spectroscopic studies confirmed that both hydrogen bonding between peptide segments and π-π stacking between BTBT chromophores are responsible for the formation of the 3D fibrillar network observed by transmission electron microscopy. The hydrogel was successfully deposited on gold interdigitated electrodes and a conductivity up to 1.6 (±0.1) × 10-5 S cm-1 was measured.

Selective Ion Sensing in Artificial Sweat Using Low-Cost Reduced Graphene Oxide Liquid-Gated Plastic Transistors.

Health monitoring is experiencing a radical shift from clinic-based to point-of-care and wearable technologies, and a variety of nanomaterials and transducers have been employed for this purpose. 2D materials (2DMs) hold enormous potential for novel electronics, yet they struggle to meet the requirements of wearable technologies. Here, aiming to foster the development of 2DM-based wearable technologies, reduced graphene oxide (rGO)-based liquid-gated transistors (LGTs) for cation sensing in artificial sweat endowed with distinguished performance and great potential for scalable manufacturing is reported. Laser micromachining is employed to produce flexible transistor test patterns employing rGO as the electronic transducer. Analyte selectivity is achieved by functionalizing the transistor channel with ion-selective membranes (ISMs) via a simple casting method. Real-time monitoring of K+ and Na+ in artificial sweat is carried out employing a gate voltage pulsed stimulus to take advantage of the fast responsivity of rGO. The sensors show excellent selectivity toward the target analyte, low working voltages (<0.5 V), fast (5-15 s), linear response at a wide range of concentrations (10 µm to 100 mm), and sensitivities of 1 µA/decade. The reported strategy is an important step forward toward the development of wearable sensors based on 2DMs for future health monitoring technologies.

Universal Fabrication of Highly Efficient Plasmonic Thin-Films for Label-Free SERS Detection.

The development of novel, highly efficient, reliable, and robust surface enhanced Raman scattering (SERS) substrates containing a large number of hot spots with programmed size, geometry, and density is extremely interesting since it allows the sensing of numerous (bio-)chemical species. Herein, an extremely reliable, easy to fabricate, and label-free SERS sensing platform based on metal nanoparticles (NPs) thin-film is developed by the layer-by-layer growth mediated by polyelectrolytes. A systematic study of the effect of NP composition and size, as well as the number of deposition steps on the substrate's performance, is accomplished by monitoring the SERS enhancement of 1-naphtalenethiol (532 nm excitation). Distinct evidence of the key role played by the interlayer (poly(diallyldimethylammonium chloride) (PDDA) or PDDA-functionalized graphene oxide (GO@PDDA)) on the overall SERS efficiency of the plasmonic platforms is provided, revealing in the latter the formation of more uniform hot spots by regulating the interparticle distances to 5 ± 1 nm. The SERS platform efficiency is demonstrated via its high analytical enhancement factor (≈106 ) and the detection of a prototypical substance(tamoxifen), both in Milli-Q water and in a real matrix, viz. tap water, opening perspectives towards the use of plasmonic platforms for future high-performance sensing applications.

How to Turn an Electron Transfer Protein into a Redox Enzyme for Biosensing.

Cytochrome c is a small globular protein whose main physiological role is to shuttle electrons within the mitochondrial electron transport chain. This protein has been widely investigated, especially as a paradigmatic system for understanding the fundamental aspects of biological electron transfer and protein folding. Nevertheless, cytochrome c can also be endowed with a non-native catalytic activity and be immobilized on an electrode surface for the development of third generation biosensors. Here, an overview is offered of the most significant examples of such a functional transformation, carried out by either point mutation(s) or controlled unfolding. The latter can be induced chemically or upon protein immobilization on hydrophobic self-assembled monolayers. We critically discuss the potential held by these systems as core constituents of amperometric biosensors, along with the issues that need to be addressed to optimize their applicability and response.

Prenylated Trans-Cinnamic Esters and Ethers against Clinical Fusarium spp.: Repositioning of Natural Compounds in Antimicrobial Discovery.

Onychomycosis is a common nail infection mainly caused by species belonging to the F. oxysporum, F. solani, and F. fujikuroi species complexes. The aim of this study was to evaluate the in vitro susceptibility of six representative strains of clinically relevant Fusarium spp. toward a set of natural-occurring hydroxycinnamic acids and their derivatives with the purpose to develop naturally occurring products in order to cope with emerging resistance phenomena. By introducing a prenylated chain at one of the hydroxy groups of trans-cinnamic acids 1-3, ten prenylated derivatives (coded 4-13) were preliminarily investigated in solid Fusarium minimal medium (FMM). Minimal inhibitory concentration (MIC) and lethal dose 50 (LD50) values were then determined in liquid FMM for the most active selected antifungal p-coumaric acid 3,3'-dimethyl allyl ester 13, in comparison with the conventional fungicides terbinafine (TRB) and amphotericin B (AmB), through the quantification of the fungal growth. Significant growth inhibition was observed for prenylated derivatives 4-13, evidencing ester 13 as the most active. This compound presented MIC and LD50 values (62-250 µM and 7.8-125 µM, respectively) comparable to those determined for TRB and AmB in the majority of the tested pathogenic strains. The position and size of the prenylated chain and the presence of a free phenol OH group appear crucial for the antifungal activity. This work represents the first report on the activity of prenylated cinnamic esters and ethers against clinical Fusarium spp. and opens new avenues in the development of alternative antifungal compounds based on a drug repositioning strategy.

On-surface synthesis of extended linear graphyne molecular wires by protecting the alkynyl group.

In this paper we report on the use of an Ullmann-like aryl halide homocoupling reaction to obtain long Graphyne Molecular Wires (GY MWs) organized in dense, ordered arrays. Instead of using highly reactive terminal alkynes, we resort to a precursor wherein the acetylenic functional group is internal, namely protected by two phenyl rings, each bearing a Br atom in the para position to allow for linear homocoupling. In addition, two further factors concur with the production of dense and highly ordered arrays of very long GY MWs, namely the geometric compatibility between the substrate and both the organometallic intermediates and the final polymeric products of the synthesis, coupled with the presence of surface-adsorbed bromine atoms separating the MWs, which minimize inter-wire cross-linking secondary reactions.

Fluid Mixing for Low-Power 'Digital Microfluidics' Using Electroactive Molecular Monolayers.

A switchable electrode, which relies on an indium-tin oxide conductive substrate coated with a self-assembled monolayer terminated with an anthraquinone group (AQ), is reported as an electrowetting system. AQ electrochemical features confer the capability of yielding a significant modulation of surface wettability as high as 26° when its redox state is switched. Hence, an array of planar electrodes for droplets actuation is fabricated and integrated in a microfluidic device to perform mixing and dispensing on sub-nanoliter scale. Vehiculation of cells across microfluidic compartments is made possible by taking full advantage of surface electrowetting in culture medium.

Tailoring water stability of cellulose nanopaper by surface functionalization.

Cellulose nanopaper (CNP) features appealing properties, including transparency, flatness, a low thermal expansion coefficient and thermal stability, often outperforming conventional paper. However, free-standing crystalline cellulose films usually swell in water or upon moisture sorption, compromising part of their outstanding properties. This remains a major problem whenever working in a water environment is required. Freestanding cellulose nanopaper is prepared by solution casting water suspensions of cellulose nanocrystals with an average width of 10 nm and an average aspect ratio of 28, isolated from Avicel by acid hydrolysis and extensively characterized by AFM and FE-SEM measurements and GPC detection of their degree of polymerization. We demonstrate by elemental analyses, FT-IR, Raman spectroscopy, XRD measurements and water contact angle detection that wet treatment with lauroyl chloride results in surface hydrophobization of nanopaper. The hydrophobized nanopaper, C12-CNP, shows a more compact surface morphology than the starting CNP, due to the effect of chemical functionalization, and presents enhanced resistance to water, as assessed by electrochemical permeation experiments. The new hydrophobized nanopaper is a promising substrate for thin film devices designed to work in a humid environment.

Self-assembled monolayers in organic electronics.

Self-assembly is possibly the most effective and versatile strategy for surface functionalization. Self-assembled monolayers (SAMs) can be formed on (semi-)conductor and dielectric surfaces, and have been used in a variety of technological applications. This work aims to review the strategy behind the design and use of self-assembled monolayers in organic electronics, discuss the mechanism of interaction of SAMs in a microscopic device, and highlight the applications emerging from the integration of SAMs in an organic device. The possibility of performing surface chemistry tailoring with SAMs constitutes a versatile approach towards the tuning of the electronic and morphological properties of the interfaces relevant to the response of an organic electronic device. Functionalisation with SAMs is important not only for imparting stability to the device or enhancing its performance, as sought at the early stages of development of this field. SAM-functionalised organic devices give rise to completely new types of behavior that open unprecedented applications, such as ultra-sensitive label-free biosensors and SAM/organic transistors that can be used as robust experimental gauges for studying charge tunneling across SAMs.

Biorecognition in Organic Field Effect Transistors Biosensors: The Role of the Density of States of the Organic Semiconductor.

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.

Structure and vibrational properties of 1D molecular wires: from graphene to graphdiyne.

Graphyne- and graphdiyne-like model systems have attracted much attention from many structural, theoretical, and synthetic scientists because of their promising electronic, optical, and mechanical properties, which are crucially affected by the presence, abundance and distribution of triple bonds within the nanostructures. In this work, we performed the two-step bottom-up on-surface synthesis of graphyne- and graphdiyne-based molecular wires on the Au(111). We characterized their structural and chemical properties both in situ (UHV conditions) through STM and XPS and ex situ (in air) through Raman spectroscopy. By comparing the results with the well-known growth of poly(p-phenylene) wires (namely the narrowest armchair graphene nanoribbon), we were able to show how to discriminate different numbers of triple bonds within a molecule or a nanowire also containing phenyl rings. Even if the number of triple bonds can be effectively determined from the main features of STM images and confirmed by fitting the C1s peak in XPS spectra, we obtained the most relevant results from ex situ Raman spectroscopy, despite the sub-monolayer amount of molecular wires. The detailed analysis of Raman spectra, combined with density functional theory (DFT) simulations, allowed us to identify the main features related to the presence of isolated (graphyne-like systems) or at least two conjugated triple bonds (graphdiyne-like systems). Moreover, other spectral features can be exploited to understand if the chemical structure of graphyne- and graphdiyne-based nanostructures suffered unwanted reactions. As in the case of sub-monolayer graphene nanoribbons obtained by on-surface synthesis, we demonstrate that Raman spectroscopy can be used for a fast, highly sensitive and non-destructive determination of the properties, the quality and the stability of the graphyine- and graphdiyne-based nanostructures obtained by this highly promising approach.

High performance multi-purpose nanostructured thin films by inkjet printing: Au micro-electrodes and SERS substrates.

Nanostructured thin metal films are exploited in a wide range of applications, spanning from electrical to optical transducers and sensors. Inkjet printing has become a compliant technique for sustainable, solution-processed, and cost-effective thin films fabrication. Inspired by the principles of green chemistry, here we show two novel formulations of Au nanoparticle-based inks for manufacturing nanostructured and conductive thin films by using inkjet printing. This approach showed the feasibility to minimize the use of two limiting factors, namely stabilizers and sintering. The extensive morphological and structural characterization provides pieces of evidence about how the nanotextures lead to high electrical and optical performances. Our conductive films (sheet resistance equal to 10.8 ± 4.1 Ω per square) are a few hundred nanometres thick and feature remarkable optical properties in terms of SERS activity with enhancement factors as high as 107 averaged on the mm2 scale. Our proof-of-concept succeeded in simultaneously combining electrochemistry and SERS by means of real-time tracking of the specific signal of mercaptobenzoic acid cast on our nanostructured electrode.

On-Surface Synthesis and Evolution of Self-Assembled Poly(p-phenylene) Chains on Ag(111): A Joint Experimental and Theoretical Study.

The growth of controlled 1D carbon-based nanostructures on metal surfaces is a multistep process whose path, activation energies, and intermediate metastable states strongly depend on the employed substrate. Whereas this process has been extensively studied on gold, less work has been dedicated to silver surfaces, which have a rather different catalytic activity. In this work, we present an experimental and theoretical investigation of the growth of poly-p-phenylene (PPP) chains and subsequent narrow graphene ribbons starting from 4,4″-dibromo-p-terphenyl molecular precursors deposited at the silver surface. By combing scanning tunneling microscopy (STM) imaging and density functional theory (DFT) simulations, we describe the molecular morphology and organization at different steps of the growth process and we discuss the stability and conversion of the encountered species on the basis of calculated thermodynamic quantities. Unlike the case of gold, at the debromination step we observe the appearance of organometallic molecules and chains, which can be explained by their negative formation energy in the presence of a silver adatom reservoir. At the dehydrogenation temperature, the persistence of intercalated Br atoms hinders the formation of well-structured graphene ribbons, which are instead observed on gold, leading only to a partial lateral coupling of the PPP chains. We numerically derive very different activation energies for Br desorption from the Ag and Au surfaces, thereby confirming the importance of this process in defining the kinetics of the formation of molecular chains and graphene ribbons on different metal surfaces.

Reduced Graphene Oxide Electrolyte-Gated Transistor Immunosensor with Highly Selective Multiparametric Detection of Anti-Drug Antibodies.

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 (≤ 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-α), the natural circulating target of IFX.

Adsorbing surface strongly influences the pseudoperoxidase and nitrite reductase activity of electrode-bound yeast cytochrome c. The effect of hydrophobic immobilization.

The Met80Ala and Met80Ala/Tyr67Ala variants of S. cerevisiae iso-1 cytochrome c (ycc) and their adducts with cardiolipin immobilized onto a gold electrode coated with a hydrophobic self-assembled monolayer (SAM) of decane-1-thiol were studied through cyclic voltammetry and surface-enhanced resonance Raman spectroscopy (SERRS). The electroactive species - containing a six-coordinate His/His axially ligated heme and a five-coordinate His/- heme stable in the oxidized and reduced state, respectively - and the pseudoperoxidase activity match those found previously for the wt species and are only slightly affected by CL binding. Most importantly, the reduced His/- ligated form of these variants is able to catalytically reduce the nitrite ion, while electrode-immobilized wt ycc and other His/Met heme ligated variants under a variety of conditions are not. Besides the pseudoperoxidase and nitrite reductase functions, which are the most physiologically relevant abilities of these constructs, also axial heme ligation and the equilibria between conformers are strongly affected by the nature - hydrophobic vs. electrostatic - of the non-covalent interactions determining protein immobilization. Also affected are the catalytic activity changes induced by a given mutation as well as those due to partial unfolding due to CL binding. It follows that under the same solution conditions the structural and functional properties of immobilized ycc are surface-specific and therefore cannot be transferred from an immobilized system to another involving different interfacial protein-SAM interactions.

Label-free immunodetection of α-synuclein by using a microfluidics coplanar electrolyte-gated organic field-effect transistor.

The aggregation of α-synuclein is a critical event in the pathogenesis of neurological diseases, such as Parkinson or Alzheimer. Here, we present a label-free sensor based on an Electrolyte-Gated Organic Field-Effect Transistor (EGOFET) integrated with microfluidics that allows for the detection of amounts of α-synuclein in the range from 0.25 pM to 25 nM. The lower limit of detection (LOD) measures the potential of our integrated device as a tool for prognostics and diagnostics. In our device, the gate electrode is the effective sensing element as it is functionalised with anti-(α-synuclein) antibodies using a dual strategy: i) an amino-terminated self-assembled monolayer activated by glutaraldehyde, and ii) the His-tagged recombinant protein G. In both approaches, comparable sensitivity values were achieved, featuring very low LOD values at the sub-pM level. The microfluidics engineering is central to achieve a controlled functionalisation of the gate electrode and avoid contamination or physisorption on the organic semiconductor. The demonstrated sensing architecture, being a disposable stand-alone chip, can be operated as a point-of-care test, but also it might represent a promising label-free tool to explore in-vitro protein aggregation that takes place during the progression of neurodegenerative illnesses.

Tetrapodal Diazatriptycene Enforces Orthogonal Orientation in Self-Assembled Monolayers.

Conformationally rigid multipodal molecules should control the orientation and packing density of functional head groups upon self-assembly on solid supports. Common tripods frequently fail in this regard because of inhomogeneous bonding configuration and stochastic orientation. These issues are circumvented by a suitable tetrapodal diazatriptycene moiety, bearing four thiol-anchoring groups, as demonstrated in the present study. Such molecules form well-defined self-assembled monolayers (SAMs) on Au(111) substrates, whereby the tetrapodal scaffold enforces a nearly upright orientation of the terminal head group with respect to the substrate, with at least three of the four anchoring groups providing thiolate-like covalent attachment to the surface. Functionalization by condensation chemistry allows a large variety of functional head groups to be introduced to the tetrapod, paving the path toward advanced surface engineering and sensor fabrication.

Catalytic reduction of dioxygen and nitrite ion at a Met80Ala cytochrome c-functionalized electrode.

The Met80Ala variant of yeast iso-1-cytochrome c, immobilized on a gold electrode, is found to exchange electrons efficiently with it in nondenaturing conditions and to provide robust and persistent catalytic currents for O 2 and nitrite ion reduction from pH 3 to 11. Direct covalent protein linkage to gold yields the best electrochemical and electrocatalytic performances without drastically affecting the structural properties of the bound protein compared to the freely diffusing species. Therefore, this biocatalytic interface can be of use for the amperometric detection of the above species, which are of great environmental, industrial, and clinical interest, with particular reference to the exploitation in nanostructured biosensing devices. This work shows that the use of a small engineered electron transfer (ET) protein, featuring an axial heme iron coordination position available for the binding of exogenous ligands, in place of a large heme enzyme is a viable strategy for the improvement of the heterogeneous ET rate and the stability and efficiency of sensing gold-protein interfaces over a wide range of T and pH.

Electron transfer and electrocatalytic properties of the immobilized methionine80alanine cytochrome c variant.

The M80A variant of yeast iso-1-cytochrome c (cytc), which features a noncoordinating Ala residue in place of the axial heme iron Met ligand, was chemisorbed on a gold electrode coated with 4-mercaptopyridine or carboxyalkanethiol self-assembled monolayers (SAM) and investigated by cyclic voltammetry at varying conditions of temperature, pH, and O2 concentration. The E degrees ' value (standard reduction potential for the heme Fe(III)/Fe(II) couple) of M80A cytc on both SAMs is of approximately -200 mV (vs the standard hydrogen electrode, SHE) at pH 7, which is more than 400 mV lower than that of native cytochrome c in the same conditions. The thermodynamics of Fe(III) to Fe(II) reduction and the kinetics of heterogeneous electron transfer (ET) are dominated by the presence of a hydroxide ion as the sixth axial heme iron ligand above pH 6. On both SAMs, protonation of the bound hydroxide ion is mainly responsible for the changes in these parameters at low pH, since the distances of ET between the heme and the electrode are found to be independent of pH in the range of 5-11. The invariance of the electrochemical features up to pH 11 indicates that no changes in heme iron coordination occur at high pH, at variance with native cytc. Most notably, immobilized M80A cytc is found to act as an efficient biocatalyst for O2 reduction from pH 5 to 11.0. This finding makes M80A cytc a suitable candidate as a constituent of a biocatalytic interface for O2 biosensing and opens the way for the exploitation of engineered cytochrome c in the bio-based detection of chemicals of environmental and clinical interest.

Modification of the gate electrode by self-assembled monolayers in flexible electrolyte-gated organic field effect transistors: work function vs. capacitance effects.

Understanding the physics behind the operational mechanism of Electrolyte-Gated Organic Field-Effect Transistors (EGOFETs) is of paramount importance for the correct interpretation of the device response. Here, we report the systematic functionalization of the gate electrode of an EGOFET with self-assembled monolayers with a variety of dipolar moments showing that both the chemical nature and the monolayer density influence the electrical characteristics of the device.