Photo-elasticity of silk fibroin harnessing whispering gallery modes.

Silk fibroin is an important biomaterial for photonic devices in wearable systems. The functionality of such devices is inherently influenced by the stimulation from elastic deformations, which are mutually coupled through photo-elasticity. Here, we investigate the photo-elasticity of silk fibroin employing optical whispering gallery mode resonation of light at the wavelength of 1550 nm. The fabricated amorphous (Silk I) and thermally-annealed semi-crystalline structure (Silk II) silk fibroin thin film cavities display typical Q-factors of about 1.6 × 104. Photo-elastic experiments are performed tracing the TE and TM shifts of the whispering gallery mode resonances upon application of an axial strain. The strain optical coefficient K' for Silk I fibroin is found to be 0.059 ± 0.004, with the corresponding value for Silk II being 0.129 ± 0.004. Remarkably, the elastic Young's modulus, measured by Brillouin light spectroscopy, is only about 4% higher in the Silk II phase. However, differences between the two structures are pronounced regarding the photo-elastic properties due to the onset of ß-sheets that dominates the Silk II structure.

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.

3D Printed Masks for Powders and Viruses Safety Protection Using Food Grade Polymers: Empirical Tests.

The production of 3D printed safety protection devices (SPD) requires particular attention to the material selection and to the evaluation of mechanical resistance, biological safety and surface roughness related to the accumulation of bacteria and viruses. We explored the possibility to adopt additive manufacturing technologies for the production of respirator masks, responding to the sudden demand of SPDs caused by the emergency scenario of the pandemic spread of SARS-COV-2. In this study, we developed different prototypes of masks, exclusively applying basic additive manufacturing technologies like fused deposition modeling (FDM) and droplet-based precision extrusion deposition (db-PED) to common food packaging materials. We analyzed the resulting mechanical characteristics, biological safety (cell adhesion and viability), surface roughness and resistance to dissolution, before and after the cleaning and disinfection phases. We showed that masks 3D printed with home-grade printing equipment have similar performances compared to the industrial-grade ones, and furthermore we obtained a perfect face fit by customizing their shape. Finally, we developed novel approaches to the additive manufacturing post-processing phases essential to assure human safety in the production of 3D printed custom medical devices.

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.

In Vivo Phenotyping for the Early Detection of Drought Stress in Tomato.

Drought stress imposes a major constraint over a crop yield and can be expected to grow in importance if the climate change predicted comes about. Improved methods are needed to facilitate crop management via the prompt detection of the onset of stress. Here, we report the use of an in vivo OECT (organic electrochemical transistor) sensor, termed as bioristor, in the context of the drought response of the tomato plant. The device was integrated within the plant's stem, thereby allowing for the continuous monitoring of the plant's physiological status throughout its life cycle. Bioristor was able to detect changes of ion concentration in the sap upon drought, in particular, those dissolved and transported through the transpiration stream, thus efficiently detecting the occurrence of drought stress immediately after the priming of the defence responses. The bioristor's acquired data were coupled with those obtained in a high-throughput phenotyping platform revealing the extreme complementarity of these methods to investigate the mechanisms triggered by the plant during the drought stress event.

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.

An in vivo biosensing, biomimetic electrochemical transistor with applications in plant science and precision farming.

The in vivo monitoring of key plant physiology parameters will be a key enabler of precision farming. Here, a biomimetic textile-based biosensor, which can be inserted directly into plant tissue is presented: the device is able to monitor, in vivo and in real time, variations in the solute content of the plant sap. The biosensor has no detectable effect on the plant's morphology even after six weeks of continuous operation. The continuous monitoring of the sap electrolyte concentration in a growing tomato plant revealed a circadian pattern of variation. The biosensor has the potential to detect the signs of abiotic stress, and therefore might be exploited as a powerful tool to study plant physiology and to increase tomato growth sustainability. Also, it can continuously communicate the plant health status, thus potentially driving the whole farm management in the frame of smart agriculture.

Emulation with Organic Memristive Devices of Impairment of LTP Mechanism in Neurodegenerative Disease Pathology.

We explore and demonstrate the extension of the synapse-mimicking properties of memristive devices to a dysfunctional synapse as it occurs in the Alzheimer's disease (AD) pathology. The ability of memristive devices to reproduce synapse properties such as LTP, LTD, and STDP has been already widely demonstrated, and moreover, they were used for developing artificial neuron networks (perceptrons) able to simulate the information transmission in a cell network. However, a major progress would be to extend the common sense of neuromorphic device even to the case of dysfunction of natural synapses. Can memristors efficiently simulate them? We provide here evidences of the ability of emulating the dysfunctional synaptic behavior typical of the AD pathology with organic memristive devices considering the effect of the disease not only on a single synapse but also in the case of a neural network, composed by numerous synapses.

Primary cortical neurons on PMCS TiO2 films towards bio-hybrid memristive device: A morpho-functional study.

We report a comprehensive study of the biocompatibility and neurocompatibility of titanium dioxide films (TiO2) prepared by Pulsed Microplasma Cluster Source (PMCS). This technique uses supersonic pulsed beams seeded by clusters of the metal oxide synthesized in a plasma discharge. The final stoichiometry of the TiO2 thin films is tuned changing the gas mixture, achieving stoichiometric or oxygen overstoichiometric films. All the films showed consistent biocompatibility and a spontaneous absorption of poly-d-lysine (PDL) that favors the adhesion and growth of murine cortical neurons. Moreover, the bioelectrical activity of the neuronal culture grown on the TiO2 film can be modulated by changing the chemistry of the surface. This work paves the way to develop a bio-hybrid neuromorphic device, where viable nerve cells are grown directly over a titanium dioxide film showing a network of memristors.

Data on HepG2 cells changes following exposure to cadmium sulphide quantum dots (CdS QDs).

The data included in this paper are associated with the research article entitled "Markers for toxicity to HepG2 exposed to cadmium sulphide quantum dots; damage to mitochondria" (Paesano et al.) [1]. The article concerns the cytotoxic and genotoxic effects of CdS QDs in HepG2 cells and the mechanisms involved. In this dataset, changes in expression levels of candidate genes are reported, together with details concerning synthesis and properties of CdS QDs, additional information obtained through literature survey, measures of the mitochondrial membrane potential and the glutathione redox state.

Markers for toxicity to HepG2 exposed to cadmium sulphide quantum dots; damage to mitochondria.

Interaction of living organisms with quantum dots (QDs) is certainly more focused on environment and occupational exposure associated with production and release or disposal. Here, the transcription of genes involved in mitochondrial organization and function in HepG2 cells exposed to cadmium sulphide (CdS) QDs has been profiled to highlight biomarkers of exposure and effect to be tested for other cadmium based QDs. At low concentrations, exposure to CdS QDs induced only minor damage to nuclear DNA, and none to mitochondrial DNA. However, the stress caused an increase in the production of reactive oxygen species (ROS), which triggered the mitochondria-mediated intrinsic apoptotic pathway involving a cascade of transcriptomic events, finally prompting the activation of a rescue pathway. The transcriptomic analysis confirmed the involvement in the response to CdS QDs of genes related to apoptosis (AIFM2 and APAF1), oxidative stress response (OXR1 and AOX1) and autophagy (ATG3 and ATG7), as potential biomarkers. Other possible biomarkers specific for mitochondria function were LONP1 and HSPD1.

Geometrical Patterning of Super-Hydrophobic Biosensing Transistors Enables Space and Time Resolved Analysis of Biological Mixtures.

PEDOT: PSS is a conductive polymer that can be integrated into last generation Organic Electrochemical Transistor (OECT) devices for biological inspection, identification and analysis. While a variety of reports in literature demonstrated the chemical and biological sensitivity of these devices, still their ability in resolving complex mixtures remains controversial. Similar OECT devices display good time dynamics behavior but lack spatial resolution. In this work, we integrated PEDOT: PSS with patterns of super-hydrophobic pillars in which a finite number of those pillars is independently controlled for site-selective measurement of a solution. We obtained a multifunctional, hierarchical OECT device that bridges the micro- to the nano-scales for specific, combined time and space resolved analysis of the sample. Due to super-hydrophobic surface properties, the biological species in the drop are driven by convection, diffusion, and the externally applied electric field: the balance/unbalance between these forces will cause the molecules to be transported differently within its volume depending on particle size thus realizing a size-selective separation. Within this framework, the separation and identification of two different molecules, namely Cetyl Trimethyl Ammonium Bromid (CTAB) and adrenaline, in a biological mixture have been demonstrated, showing that geometrical control at the micro-nano scale impart unprecedented selectivity to the devices.

Bio-hybrid interfaces to study neuromorphic functionalities: New multidisciplinary evidences of cell viability on poly(anyline) (PANI), a semiconductor polymer with memristive properties.

The interfacing of artificial devices with biological systems is a challenging field that crosses several disciplines ranging from fundamental research (biophysical chemistry, neurobiology, material and surface science) to frontier technological application (nanotechnology, bioelectronics). The memristor is the fourth fundamental circuit element, whose electrical properties favor applications in signal processing, neural networks, and brain-computer interactions and it represents a new frontier for technological applications in many fields including the nanotechnologies, bioelectronics and the biosensors. Using multidisciplinary approaches, covering surface science, cell biology and electrophysiology, we successfully implemented a living bio-hybrid system constituted by cells adhering to films of poly(aniline) (PANI), a semiconductor polymer having memristive properties assembled with polyelectrolytes. Here we tested whether the PANI devices could support survivor, adhesion and differentiation of several cell lines, including the neuron-like SHSY5Y cells. Moreover, we performed electrophysiology on these cells showing that the biophysical properties are retained with differences occurring in the recorded ion currents. Taken together, the cell viability here reported is the key requirement to design and develop a reliable functional memristor-based bio-hybrid able to mimic neuronal activity and plasticity.

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.

PEDOT:PSS Interfaces Support the Development of Neuronal Synaptic Networks with Reduced Neuroglia Response In vitro.

The design of electrodes based on conductive polymers in brain-machine interface technology offers the opportunity to exploit variably manufactured materials to reduce gliosis, indeed the most common brain response to chronically implanted neural electrodes. In fact, the use of conductive polymers, finely tailored in their physical-chemical properties, might result in electrodes with improved adaptability to the brain tissue and increased charge-transfer efficiency. Here we interfaced poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) ( PEDOT: PSS) doped with different amounts of ethylene glycol (EG) with rat hippocampal primary cultures grown for 3 weeks on these synthetic substrates. We used immunofluorescence and scanning electron microscopy (SEM) combined to single cell electrophysiology to assess the biocompatibility of PEDOT: PSS in terms of neuronal growth and synapse formation. We investigated neuronal morphology, density and electrical activity. We reported the novel observation that opposite to neurons, glial cell density was progressively reduced, hinting at the ability of this material to down regulate glial reaction. Thus, PEDOT: PSS is an attractive candidate for the design of new implantable electrodes, controlling the extent of glial reactivity without affecting neuronal viability and function.

Titanyl phthalocyanine ambipolar thin film transistors making use of carbon nanotube electrodes.

The capability of efficiently injecting charge carriers into organic films and finely tuning their morphology and structure is crucial to improve the performance of organic thin film transistors (OTFTs). In this work, we investigate OTFTs employing carbon nanotubes (CNTs) as the source-drain electrodes and, as the organic semiconductor, thin films of titanyl phthalocyanine (TiOPc) grown by supersonic molecular beam deposition (SuMBD). While CNT electrodes have shown an unprecedented ability to improve charge injection in OTFTs, SuMBD is an effective technique to tune film morphology and structure. Varying the substrate temperature during deposition, we were able to grow both amorphous (low substrate temperature) and polycrystalline (high substrate temperature) films of TiOPc. Regardless of the film morphology and structure, CNT electrodes led to superior charge injection and transport performance with respect to benchmark Au electrodes. Vacuum annealing of polycrystalline TiOPc films with CNT electrodes yielded ambipolar OTFTs.

Growth dynamics in supersonic molecular beam deposition of pentacene sub-monolayers on SiO2.

Studying highly energetic pentacene impinging on a surface, we demonstrated that the perpendicular component of the momentum drives the dynamics of molecule-molecule interactions and hence the island nucleation process, while the parallel component governs the dynamics of the interactions between the surface and the molecule and therefore determines the sticking coefficient and the island fractality.