Publications

Over the last decade, 3D-printed porous calcium phosphates have emerged in the market for customized bone reconstruction. However, despite their excellent biological properties, the inherent brittleness is an obstacle that limits their clinical applications, as the scaffolds must withstand the surgical procedures and the mechanical stresses once implanted. Low-temperature self-hardening calcium phosphate inks offer unique possibilities to be reinforced with polymers, as they do not require high-temperature treatments. This study compares two routes for incorporating poly (lactic-co-glycolic acid) (PLGA) into 3D-printed calcium phosphate scaffolds: i) the use of a PLGA solution as a binder in an alpha-tricalcium phosphate self-hardening ink; ii) the infiltration of a PLGA solution into previously hardened 3D-printed calcium-deficient hydroxyapatite scaffolds. The influence of the added PLGA on the physical-chemical properties, mechanical performance and in vitro biological properties is assessed using a commercially available biomimetic calcium phosphate scaffold as a control. The addition of PLGA increases the plastic deformation capacity and the strength, both in compression and bending, and significantly improves the work of fracture of the scaffolds, up to an 8-fold in compression when PLGA is incorporated as a binder in the ink. Moreover, screwability tests demonstrate the enhanced fixability of the composite scaffolds in a knife-edge ridge indication with challenging fixation in the jaw. Importantly, the improvement of the mechanical properties by the addition of PLGA does not impair the good cytocompatibility of the material. Regarding the two routes studied, the PLGA incorporation in the ink is the best option in terms of overall improvement of the mechanical performance and osteogenic cell response.

JTD Keywords: Alkaline-phosphatase, B. composites, C. mechanical properties, Composite scaffold, D. apatite, Differentiation, E. biomedical application, In-vivo, Join, Regeneration

Bacterial infection remains a significant problem associated with orthopaedic surgeries leading to surgical site infection (SSI). This unmet medical need can become an even greater complication when surgery is due to malignant bone tumor. In the present study, we evaluated in vitro titanium (Ti) implants subjected to gallium (Ga) and silver (Ag)-doped thermochemical treatment as strategy to prevent SSI and improve osteointegration in bone defects caused by diseases such as osteoporosis, bone tumor, or bone metastasis. Firstly, as Ga has been reported to be an osteoinductive and anti-resorptive agent, its performance in the mixture was proved by studying human mesenchymal stem cells (hMSC) and pre-osteoclasts (RAW264.7) behaviour. Then, the antibacterial potential provided by Ag was assessed by resembling "The Race for the Surface" between hMSC and Pseudomonas aeruginosa in two co-culture methods. Moreover, the presence of quorum sensing molecules in the co-culture was evaluated. The results highlighted the suitability of the mixture to induce osteodifferentiation and reduce osteoclastogenesis in vitro . Furthermore, the GaAg surface promoted strong survival rate and retained osteoinduction potential of hMSCs even after bacterial inoculation. Therefore, GaAg-modified titanium may be an ideal candidate to repair bone defects caused by excessive bone resorption, in addition to preventing SSI.

JTD Keywords: Antibacteria, Antibacterial, Bone resorption, Expression, Gallium, In-vitro, Ligan, Nf-kappa-b, Nfatc1, Osteoclast formation, Phosphatase, Receptor activator, Silver, Ti metal, Titanium

Micro/nanomotors (MNMs) have evolved from single self-propelled entities to versatile systems capable of performing one or multiple biomedical tasks. When single MNMs self-assemble into coordinated swarms, either under external control or triggered by chemical reactions, they offer advantages that individual MNMs cannot achieve. These benefits include intelligent multitasking and adaptability to changes in the surrounding environment. Here, we provide our perspective on the evolution of MNMs, beginning with the development of enzymatic MNMs since the first theoretical model was proposed in 2005. These enzymatic MNMs hold immense promise in biomedicine due to their advantages in biocompatibility and fuel availability. Subsequently, we introduce the design and application of single motors in biomedicine, followed by the control of MNM swarms and their biomedical applications. In the end, we propose viable solutions for advancing the development of MNM swarms and anticipate valuable insights into the creation of more intelligent and controllable MNM swarms for biomedical applications.; Micro/nanomotor swarms propelled by diverse mechanisms.

JTD Keywords: Active particles, Actuation, Behaviors, Biocompatibility, Biomedical applications, Coordination reactions, Design and application, Diffusion, External control, Medical applications, Micromotors, Motion, Nanomotors, Powered nanomotors, Propulsion, Self-assemble, Surrounding environment, Theoretical modeling, Versatile system, Viable solutions

Applications of sodium alginate (Alg) and polyacrylic acid (PAA) hydrogels in biomedicine are well-known. These are predefined by the strength and weakness of their properties, which in turn depend on the chemical structure and the architecture of their crosslinks. In this work, Alg biopolymer has been grafted to synthetic PAA that has been chemically crosslinked using N,N '-methylene-bisacrylamide (MBA) to produce a pH responsive hydrogel with adhesive property. The double crosslinking network, which combines MBA-mediated covalent crosslinks and ionic crosslinks in Alg domains, results in an elastic modulus that resembles that of highly anisotropic and viscoelastic human skin. After addressing the influence of the dual network onto the Alg-g-PAA hydrogel properties, a prospection of its potential as an adhesive has been made considering different surfaces (rubber, paper steel, porcine skin, etc). The bonding energy onto porcine skin, 32.6 +/- 4.6 J/m2, revealed that the Alg-g-PAA hydrogel can be proposed in the biomedical field as tissue adhesive for wound healing applications. Finally, the hydrogel has been semi-interpenetrated with poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH) chains through a chemical oxidative polymerization process. The resulting hydrogel, Alg-g- PAA/PEDOT-MeOH, which is even more porous than Alg-g-PAA, in addition to being electro-responsive, maintains adhesive properties.

JTD Keywords: Adhesion properties, Adhesion properties,biomedical applications,bonding energy,dual network,conducting hydrogel, Adhesive properties, Adhesives, Biomedical applications, Biopolymers, Bonding energies, Bonding energy, Chemical bonds, Conducting hydrogels, Crosslinking, Dual network, Hydrogels, Medical applications, Methylenebisacrylamide, Poly(acrylic acid), Porcine skin, Property, Rational design,film, Sodium alginate

[No abstract available]

JTD Keywords: Breathing, Cost, Developed country, Developing countries, Developing country, Health care facility, Home monitoring, Human, Humans, Internet, Internet of things, Letter, Lowest income group, Lung function, Lung mechanics, Lung resistance, Mathematical model, Middle income country, Mobile applications, Non invasive procedure, Open source technology, Oscillometry, Pneumotachygraphy, Telemedicine

The performance of single-chain polymeric nanoparticles (SCPNs) in biomedical applications highly depends on their conformational stability in cellular environments. Until now, such stability studies are limited to 2D cell culture models, which do not recapitulate the 3D tumor microenvironment well. Here, a microfluidic tumor-on-a-chip model is introduced that recreates the tumor milieu and allows in-depth insights into the diffusion, cellular uptake, and stability of SCPNs. The chip contains Matrigel/collagen-hyaluronic acid as extracellular matrix (ECM) models and is seeded with cancer cell MCF7 spheroids. With this 3D platform, it is assessed how the polymer's microstructure affects the SCPN's behavior when crossing the ECM, and evaluates SCPN internalization in 3D cancer cells. A library of SCPNs varying in microstructure is prepared. All SCPNs show efficient ECM penetration but their cellular uptake/stability behavior depends on the microstructure. Glucose-based nanoparticles display the highest spheroid uptake, followed by charged nanoparticles. Charged nanoparticles possess an open conformation while nanoparticles stabilized by internal hydrogen bonding retain a folded structure inside the tumor spheroids. The 3D microfluidic tumor-on-a-chip platform is an efficient tool to elucidate the interplay between polymer microstructure and SCPN's stability, a key factor for the rational design of nanoparticles for targeted biological applications.© 2024 The Authors. Small Methods published by Wiley-VCH GmbH.

JTD Keywords: 3d cancer cell uptake, Cancer cells, Cell culture, Cell uptake, Cellular uptake, Diseases, Ecm penetration, Extracellular matrices, Extracellular matrix penetration, Functional polymers, Hydrogen bonds, Medical applications, Microfluidics, Microstructure, Nanoparticles, Polymeric nanoparticles, Scpns, Single chains, Single-chain polymeric nanoparticle, Stability, Tumor-on-a-chip, Tumors

A new generation of fully bioresorbable metallic Zn-based alloys could be used for stenting applications; however, the initial surface degradation delays stent re-endothelialization. Thus, this work proposes a dual strategy to control the corrosion and accelerate the endothelialization of ZnMg and ZnAg biodegradable alloys. First, a stable polycaprolactone (PCL) coating is obtained and followed by its functionalization with either linear RGD (Arg-Gly-Asp) or REDV (Arg-Glu-Asp-Val) peptides or a dual peptide-based platform combining both sequences (RGD-REDV). Scratching tests showed neither delamination nor detachment of the polymeric coating. Potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) measurements confirmed the corrosion resistance after PCL coating by revealing lower current density and higher absolute impedance values. X-ray photoelectron spectroscopy (XPS) and fluorescent microscopy confirmed the correct peptide immobilization onto PCL coated Zn alloys. The functionalized samples exhibited enhanced human umbilical vein endothelial cells (HUVEC) adhesion. The higher number of adhered cells to the functionalized surfaces with the RGD-REDV platform demonstrates the synergistic effect of combining both RGD and REDV sequences. Higher corrosion resistance together with enhanced endothelialization indicates that the dual functionalization of Zn alloys with PCL and peptide-based RGD-REDV platform holds great potential to overcome the clinical limitations of current biodegradable metal stents.

JTD Keywords: Binary alloys, Biodegradable metals, Bioresorbable, Cardiovascular applications, Cell adhesive peptides, Corrosion, Corrosion resistance, Corrosion resistant alloys, Corrosion resistant coatings, Degradation, Dual peptide-based platform, Electrochemical corrosion, Electrochemical impedance spectroscopy, Endothelial cells, Endothelialization, Functionalization, Functionalizations, In-vitro, Magnesium alloys, Metallics, Mg alloy, Peptides, Polycaprolactone coating, Polymer-coatings, Rgd-functionalization, Silver alloys, Stents, Surface, X ray photoelectron spectroscopy, Zinc, Zinc alloys, Zn alloys, Zn-based alloys

Polymeric membranes exhibit unique and modulate transport properties when they are properly functionalised, which make them ideal for ions transport, molecules separation and molecules interactions. The present work proposes the design and fabrication of nanostructured membranes, composed by biodegradable poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), incorporating a lipophilic molecule (cholesterol) covalently bonded, were especially designed to provide even more application opportunities in sensors field. Electrochemical studies, by means of electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV), revealed important differences regarding the functionalised and non-functionalised PLA systems. PEGcholesterol building block units showed a clear affinity with ascorbic acid (vitamin C) and Trolox (R) (a watersoluble analogue of vitamin E), both hydrophilic in nature, with a limit of detection capacity of 8.12 mu M for AA and 3.53 mu M for AA and Trolox, respectively, in aqueous salt solution. The bioinspired polymer may be used to incorporate antioxidant property that allow the design of anti-stress biosensors, electrodes for the detection of vitamin C or vitamin E in biomedical nutrition programs, among other applications.

JTD Keywords: Antioxidant molecules, Antioxidants, Application programs, Ascorbic acid, Biomimetics, C (programming language), Capacity, Chemical detection, Cholesterol, Cyclic voltammetry, Electrochemical detection, Electrochemical impedance spectroscopy, Functional polymers, Functionalized, Lactic acid, Molecules, Nanomembranes, Poly ethylene glycols, Poly lactic acid, Poly(ethylene glycol), Poly(ethyleneglycol), Poly(lactic acid), Polyethylene glycols, Vitamin-e

Clathrin-mediated endocytosis (CME) is an essential cellular process, conserved among eukaryotes. Yeast constitutes a powerful genetic model to dissect the complex endocytic machinery, yet there is a lack of specific pharmacological agents to interfere with CME in these organisms. TL2 is a light-regulated peptide inhibitor targeting the AP2-β-adaptin/β-arrestin interaction and that can photocontrol CME with high spatiotemporal precision in mammalian cells. Here, we study endocytic protein dynamics by live-cell imaging of the fluorescently tagged coat-associated protein Sla1-GFP, demonstrating that TL2 retains its inhibitory activity in S. cerevisiae spheroplasts. This is despite the β-adaptin/β-arrestin interaction not being conserved in yeast. Our data indicate that the AP2 α-adaptin is the functional target of activated TL2. We identified as interacting partners for the α-appendage, the Eps15 and epsin homologues Ede1 and Ent1. This demonstrates that endocytic cargo loading and sensing can be executed by conserved molecular interfaces, regardless of the proteins involved.© 2023 The Author(s).

JTD Keywords: adapters, alpha-appendage, azobenzene, cross-linker, mechanism, peptides, proteins, receptor, trafficking, Actin polymerization, Biochemistry, Biological sciences, Cell biology, Molecular biology, Natural sciences

Electrochemically responsive hydrogel networks have been obtained usin g printable inks made of a biopolymer, alginate (Alg), and an inorganic 2D material , MXene (titaniu m carbide, Ti3C2Tx) nanosheets. While MXene offers an electrically conductive pathway for electron transfer and Alg provides an interconnected framework for ion diffusion, the printed nanocomposite results, after gelation, in an extended active interface for redox reactions, being an ideal framework to design and construct flexible devices for biomedical applications. In this work, after characterization, we demonstrate that hydrogels obtained by cross-linking printed Alg /MXene inks exhibit great potential for bioelectronics. More specifically, we prove that flexible Alg/MXene hydrogels act as self-supported electroactive electrodes for the electrochemical detection of bioanalytes, such as dopamine, with a performance similar to that achieved using more sophisticated electrodes, as for example those containing conducting poly-mers and electrocatalytic gold nanoparticles. In addition, Alg/MXene hydrogels have been successfully used to regulate the release of a previously loaded broad spectrum antibiotic (chloramphenicol) by electrical stimulation.

JTD Keywords: 3d-printing, Biomedical application s, Composites, Conducting polymers, Drug release, Electroresponsive hydrogels, Fabrication, Hydrogels, Platform, Sensors, Strategy, Surface, Thin-film, Titanium carbide

Drug and gene delivery systems based on polymeric nanoparticles offer a greater efficacy and a reduced toxicity compared to traditional formulations. Recent studies have evidenced that their internalization, biodistribution and efficacy can be affected, among other factors, by their mechanical properties. Here, we analyze by means of Atomic Force Microscopy force spectroscopy how composition, surface functionalization and loading affect the mechanics of nanoparticles. For this purpose, nanoparticles made of Poly(lactic-co-glycolic) (PLGA) and Ethyl cellulose (EC) with different functionalizations and loading were prepared by nano-emulsion templating using the Phase Inversion Composition method (PIC) to form the nano-emulsions. A multiparametric nanomechanical study involving the determination of the Young's modulus, maximum deformation and breakthrough force was carried out. The obtained results showed that composition, surface functionalization and loading affect the nanomechanical properties in a different way, thus requiring, in general, to consider the overall mechanical properties after the addition of a functionalization or loading. A graphical representation method has been proposed enabling to easily identify mechanically equivalent formulations, which is expected to be useful in the development of soft polymeric nanoparticles for pre-clinical and clinical use.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

JTD Keywords: afm, atomic-force microscopy, cell, delivery-systems, drug-delivery, emulsification approach, internalization, mechanics of nanoparticles, nanomedicine, nanoparticle functionalization, particles, protein corona, size, young?s modulus, Afm, Loaded plga nanoparticles, Mechanics of nanoparticles, Nanomedicine, Nanoparticle functionalization, Polymeric nanoparticles, Young’s modulus

This manuscript presents portable and low cost electronic system for specific point-of-use dielectrophoresis applications. The system is composed of two main modules: a) a multiphase generator based on a Class E amplifier, which provides 4 sinusoidal signals (0°, 90°, 180°, 270°) at 1 MHz with variable output voltage up to 10 Vpp (Vm) and an output driving current of 1 A; and b) a dielectrophoresis-based microfluidic chip containing two interdigitated electrodes. The system has been validated by concentrating Escherichia Coli at 1 MHz while applying a continuous flow of 5 ?L/min. Device functionalities were verified under different conditions achieving a 83% trapping efficiency in the best case. © Springer International Publishing Switzerland 2014.

JTD Keywords: bacteria, emulsifier, enterobacter, exopolysaccharide, Bacteria, Bacteria concentrations, Biochemical engineering, Cell concentrator, Class e amplifier, Class-e amplifier, Device functionality, Dielectrophoresis, Electronic equipment, Electronics, Electrophoresis, Emulsifier, Enterobacter, Escherichia coli, Exopolysaccharide, Inter-digitated electrodes, Lab-on-a-chip (loc), Low cost, Low costs, Low-cost electronics, Medical computing, Monosaccharide, Portable device, Power amplifiers, Trapping efficiencies

Yeast genetics made it possible to derive the first fundamental insights into prion composition, conformation, and propagation. Fast-forward 30 years and the same model organism is now proving an extremely powerful tool to comprehensively explore the impact of mutations in prion sequences on their function, toxicity, and physical properties. Here, we provide an overview of novel multiplexed strategies where deep mutagenesis is combined to a range of tailored selection assays in yeast, which are particularly amenable for investigating prions and prion-like sequences. By mimicking evolution in a flask, these multiplexed approaches are revealing mechanistic insights on the consequences of prion self-assembly, while also reporting on the structure prion sequences adopt in vivo.Copyright © 2022 Elsevier Ltd. All rights reserved.

JTD Keywords: aggregation, appearance, domains, inheritance, mutations, nucleation, physical basis, propagation, protein, Phase-separation

Remarkable progress in bioengineering over the past two decades has enabled the formulation of fundamental design principles for a variety of medical and non-medical applications. These advancements have laid the foundation for building multicellular engineered living systems (M-CELS) from biological parts, forming functional modules integrated into living machines. These cognizant design principles for living systems encompass novel genetic circuit manipulation, self-assembly, cell–cell/matrix communication, and artificial tissues/organs enabled through systems biology, bioinformatics, computational biology, genetic engineering, and microfluidics. Here, we introduce design principles and a blueprint for forward production of robust and standardized M-CELS, which may undergo variable reiterations through the classic design-build-test-debug cycle. This Review provides practical and theoretical frameworks to forward-design, control, and optimize novel M-CELS. Potential applications include biopharmaceuticals, bioreactor factories, biofuels, environmental bioremediation, cellular computing, biohybrid digital technology, and experimental investigations into mechanisms of multicellular organisms normally hidden inside the “black box” of living cells.

JTD Keywords: cell-fate specification, endothelial-cells, escherichia-coli, extracellular-matrix, gene-expression noise, nuclear hormone-receptors, pluripotent stem-cells, primitive endoderm, transcription factors, Artificial tissues, Assembly cells, Biological parts, Biological systems, Bioremediation, Blood-brain-barrier, Cell engineering, Cell/matrix communication, Design principles, Environmental technology, Functional modules, Fundamental design, Genetic circuits, Genetic engineering, Living machines, Living systems, Medical applications, Molecular biology, Synthetic biology

JTD Keywords: amino-acids, catalysis, dopant-free hydroxyapatite, electrical properties, electrophotosynthesis, nitrogen, thermally-stimulated polarization, Advanced materials, Biocompatibility, Biomedical applications, Brushite, Doped hydroxyapatites, Electric voltage, Electrical characterization, Electrochemical impedance spectroscopy, Equivalent circuits, Future perspectives, Highest temperature, Hydroxyapatite, Interfaces (materials), Material interfaces, Medical applications, Polarization, Polarization conditions, Surface-charges, Technological applications

The use of silver nanoparticles (Ag NPs) in the biomedical field deserves a mindful analysis of the possible inflammatory response which could limit their use in the clinic. Despite the anti-cancer properties of Ag NPs having been widely demonstrated, there are still few studies concerning their involvement in the activation of specific inflammatory pathways. The inflammatory outcome depends on the synthetic route used in the NPs production, in which toxic reagents are employed. In this work, we compared two types of Ag NPs, obtained by two different chemical routes: conventional synthesis using sodium citrate and a green protocol based on leaf extracts as a source of reduction and capping agents. A careful physicochemical characterization was carried out showing spherical and stable Ag NPs with an average size between 20 nm and 35 nm for conventional and green Ag NPs respectively. Then, we evaluated their ability to induce the activation of inflammation in Human Leukemic Monocytes (THP-1) differentiated into M0 macrophages using 1 µM and 2 µM NPs concentrations (corresponded to 0.1 µg/mL and 0.2 µg/mL respectively) and two-time points (24 h and 48 h). Our results showed a clear difference in Nuclear Factor ?B (NF-?b) activation, Interleukins 6–8 (IL-6, IL-8) secretion, Tumor Necrosis Factor-? (TNF-?) and Cyclooxygenase-2 (COX-2) expression exerted by the two kinds of Ag NPs. Green Ag NPs were definitely tolerated by macrophages compared to conventional Ag NPs which induced the activation of all the factors mentioned above. Subsequently, the exposure of breast cancer cell line (MCF-7) to the green Ag NPs showed that they exhibited antitumor activity like the conventional ones, but surprisingly, using the MCF-10A line (not tumoral breast cells) the green Ag NPs did not cause a significant decrease in cell viability. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

JTD Keywords: activation, biosynthesis, gold nanoparticles, green route, inflammation response, mechanism, metal, nanotechnology, physico-chemical properties, raman-spectroscopy, resonance, silver nanoparticles, surface, Biomedical fields, Cell culture, Cell death, Chemical activation, Chemical routes, Conventional synthesis, Diseases, Green route, Inflammation response, Inflammatory response, Macrophages, Metal nanoparticles, Nf-kappa-b, Pathology, Physico-chemical properties, Physicochemical property, Property, Silver nanoparticles, Sodium compounds, Synthetic routes, Toxic reagents

JTD Keywords: Experimental approaches, Monitoring, Pneumonia

Poor sleep quality or disturbed sleep is associated with multiple health conditions. Sleep position affects the severity and occurrence of these complications, and positional therapy is one of the less invasive treatments to deal with them. Sleep positions can be self-reported, which is unreliable, or determined by using specific devices, such as polysomnography, polygraphy or cameras, that can be expensive and difficult to employ at home. The aim of this study is to determine how smartphones could be used to monitor and treat sleep position at home. We divided our research into three tasks: (1) develop an Android smartphone application (‘SleepPos’ app) which monitors angle-based high-resolution sleep position and allows to simultaneously apply positional treatment; (2) test the smartphone application at home coupled with a pulse oximeter; and (3) explore the potential of this tool to detect the positional occurrence of desaturation events. The results show how the ‘SleepPos’ app successfully determined the sleep position and revealed positional patterns of occurrence of desaturation events. The ‘SleepPos’ app also succeeded in applying positional therapy and preventing the subjects from sleeping in the supine sleep position. This study demonstrates how smartphones are capable of reliably monitoring high-resolution sleep position and provide useful clinical information about the positional occurrence of desaturation events.

JTD Keywords: accelerometry, android, apnea patients, app, association, biomedical signal processing, management, mhealth, monitoring, pathophysiology, pilot mhealth, questionnaire, sleep position, smartphone, supine position, time, Accelerometry, Android, App, Biomedical signal processing, Mhealth, Monitoring, Sleep position, Smart-phone, Smartphone, Tennis ball technique

Mapping the biochemical composition of eukaryotic cells without the use of exogenous labels is a long-sought objective in cell biology. Recently, it has been shown that composition maps on dry single bacterial cells with nanoscale spatial resolution can be inferred from quantitative nanoscale dielectric constant maps obtained with the scanning dielectric microscope. Here, it is shown that this approach can also be applied to the much more challenging case of fixed and dry eukaryotic cells, which are highly heterogeneous and show micrometric topographic variations. More importantly, it is demonstrated that the main bottleneck of the technique (the long computation times required to extract the nanoscale dielectric constant maps) can be shortcut by using supervised neural networks, decreasing them from weeks to seconds in a wokstation computer. This easy-to-use data-driven approach opens the door for in situ and on-the-fly label free nanoscale composition mapping of eukaryotic cells with scanning dielectric microscopy. © 2021 The Authors. Small Methods published by Wiley-VCH GmbH

JTD Keywords: eukaryotic cells, label-free mapping, machine learning, nanoscale, scanning dielectric microscopy, Biochemical composition, Cells, Constant, Cytology, Data-driven approach, Dielectric forces, Dielectric materials, Eukaryotic cells, Label-free mapping, Machine learning, Mapping, Microscopy, atomic force, Nanoscale, Nanoscale composition, Nanoscale spatial resolution, Nanotechnology, Scanning, Scanning dielectric microscopy, Supervised neural networks

Flexible electrochemical sensors based on electroactive materials have emerged as powerful analytical tools for biomedical applications requiring bioanalytes detection. Within this context, 3D printing is a remarkable technology for developing electrochemical devices, due to no design constraints, waste minimization, and batch manufacturing with high reproducibility. However, the fabrication of 3D printed electrodes is still limited by the in-house fabrication of conductive filaments, which requires the mixture of the electroactive material with melted of thermoplastic polymer (e.g., polylactic acid, PLA). Herein, a simple approach is presented for preparing electrochemical dopamine (DA) biosensors. Specifically, the surface of 3D-printed PLA specimens, which exhibit an elastic modulus and a tensile strength of 3.7 +/- 0.3 GPa and 47 +/- 1 MPa, respectively, is activated applying a 0.5 m NaOH solution for 30 min and, subsequently, poly(3,4-ethylenedioxythiophene) is polymerized in situ using aqueous solvent. The detection of DA with the produced sensors has been demonstrated by cyclic voltammetry, differential pulse voltammetry, and chronoamperometry. In summary, the obtained results reflect that low-cost electrochemical sensors, which are widely used in medicine and biotechnology, can be rapidly fabricated using the proposed approach that, although based on additive manufacturing, does not require the preparation of conductive filaments.

JTD Keywords: 3d printers, Additive manufacturing, Amines, Batch manufacturing, Biomedical applications, Chronoamperometry, Conducting polymer, Conducting polymers, Conductive filaments, Conservation, Cyclic voltammetry, Differential pulse voltammetry, Electroactive material, Electrochemical biosensor, Electrochemical devices, Electrochemical sensors, Electrodes, Electron emission, Flexible electrode, High reproducibility, Medical applications, Neurophysiology, Poly-3 ,4-ethylenedioxythiophene, Polyesters, Polylactic aci, Sodium hydroxide, Tensile strength, Thermoplastic polymer

Wastewater treatment plants (WWTPs) are sources of greenhouse gases, hazardous air pollutants and offensive odors. These emissions can have negative repercussions in and around the plant, degrading the quality of life of surrounding neighborhoods, damaging the environment, and reducing employee’s overall job satisfaction. Current monitoring methodologies based on fixed gas detectors and sporadic olfactometric measurements (human panels) do not allow for an accurate spatial representation of such emissions. In this paper we use a small drone equipped with an array of electrochemical and metal oxide (MOX) sensors for mapping odorous gases in a mid-sized WWTP. An innovative sampling system based on two (10 m long) flexible tubes hanging from the drone allowed near-source sampling from a safe distance with negligible influence from the downwash of the drone’s propellers. The proposed platform is very convenient for monitoring hard-toreach emission sources, such as the plant’s deodorization chimney, which turned out to be responsible for the strongest odor emissions. The geo-localized measurements visualized in the form of a two-dimensional (2D) gas concentration map revealed the main emission hotspots where abatement solutions were needed. A principal component analysis (PCA) of the multivariate sensor signals suggests that the proposed system can also be used to trace which emission source is responsible for a certain measurement.

JTD Keywords: air pollution, environmental monitoring, gas sensors, industrial emissions, mapping, odour, uav, Air pollution, Drone, Environmental monitoring, Gas sensors, Industrial emissions, Mapping, Odour, Sensors, Uav

© 2020 The Author(s) The dominant biomedical perspective on addictions has been that they are chronic brain diseases. While we acknowledge that the brains of people with addictions differ from those without, we argue that the “broken brain” model of addiction has important limitations. We propose that a systems-level perspective more effectively captures the integrated architecture of the embodied and situated human mind and brain in relation to the development of addictions. This more dynamic conceptualization places addiction in the broader context of the addicted brain that drives behavior, where the addicted brain is the substrate of the addicted mind, that in turn is situated in a physical and socio-cultural environment. From this perspective, neurorehabilitation should shift from a “broken-brain” to a systems theoretical framework, which includes high-level concepts related to the physical and social environment, motivation, self-image, and the meaning of alternative activities, which in turn will dynamically influence subsequent brain adaptations. We call this integrated approach system-oriented neurorehabilitation. We illustrate our proposal by showing the link between addiction and the architecture of the embodied brain, including a systems-level perspective on classical conditioning, which has been successfully translated into neurorehabilitation. Central to this example is the notion that the human brain makes predictions on future states as well as expected (or counterfactual) errors, in the context of its goals. We advocate system-oriented neurorehabilitation of addiction where the patients' goals are central in targeted, personalized assessment and intervention.

JTD Keywords: addiction, brain disease model, neurorehabilitation, Addiction, Brain disease model, Neurorehabilitation, Systems approach

Engineered immunoglobulin-G molecules (IgGs) are of wide interest for the development of detection elements in protein-based biosensors with clinical applications. The strategy usually employed for the de novo design of such engineered IgGs consists on merging fragments of the three-dimensional structure of a native IgG, which is immobilized on the biosensor surface, and of an antibody with an exquisite target specificity and affinity. In this work conventional and accelerated classical molecular dynamics (cMD and aMD, respectively) simulations have been used to propose two IgG-like antibodies for COVID-19 detection. More specifically, the crystal structure of the IgG1 B12 antibody, which inactivates the human immunodeficiency virus-1, has been merged with the structure of the antibody CR3022 Fab tightly bounded to SARS-CoV-2 receptor-binding domain (RBD) and the structure of the 5309 antibody Fab fragment complexed with SARS-CoV-2 RBD. The two constructed antibodies, named IgG1-CR3022 and IgG1-S309, respectively, have been immobilized on a stable gold surface through a linker. Analyses of the influence of both the merging strategy and the substrate on the stability of the two constructs indicate that the IgG1-S309 antibody better preserves the neutralizing structure than the IgG1-CR3022 one. Overall, results indicate that the IgG1-S309 is appropriated for the generation of antibody based sensors for COVID-19 diagnosis. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

JTD Keywords: cr3022, igg1, molecular engineering, s309, Antibodies, Antibody engineering, Biosensors, Chemical detection, Clinical application, Cov, Cr3022, Crystal structure, Design, Diseases, Gold nanoparticles, Igg1, Igg1 antibody, Immobilization, Immunoglobulin g, Immunosensor, In-silico, Merging, Molecular dynamics, Molecular engineering, Orientation, Protein-based biosensors, Receptor-binding domains, S309, Sars, Sensor, Spike protein, Target, Vaccine, Viruses

We introduce a new method, the Local Monge Parametrizations (LMP) method, to approximate tensor fields on general surfaces given by a collection of local parametrizations, e.g. as in finite element or NURBS surface representations. Our goal is to use this method to solve numerically tensor-valued partial differential equations (PDEs) on surfaces. Previous methods use scalar potentials to numerically describe vector fields on surfaces, at the expense of requiring higher-order derivatives of the approximated fields and limited to simply connected surfaces, or represent tangential tensor fields as tensor fields in 3D subjected to constraints, thus increasing the essential number of degrees of freedom. In contrast, the LMP method uses an optimal number of degrees of freedom to represent a tensor, is general with regards to the topology of the surface, and does not increase the order of the PDEs governing the tensor fields. The main idea is to construct maps between the element parametrizations and a local Monge parametrization around each node. We test the LMP method by approximating in a least-squares sense different vector and tensor fields on simply connected and genus-1 surfaces. Furthermore, we apply the LMP method to two physical models on surfaces, involving a tension-driven flow (vector-valued PDE) and nematic ordering (tensor-valued PDE), on different topologies. The LMP method thus solves the long-standing problem of the interpolation of tensors on general surfaces with an optimal number of degrees of freedom.

JTD Keywords: Approximation, Finite elements, Surface PDE, Tensor-valued PDE, Vector-valued PDE

The difficulty to obtain ground truth (i.e. empirical evidence) about how a gas disperses in an environment is one of the major hurdles in the field of mobile robotic olfaction (MRO), impairing our ability to develop efficient gas source localization strategies and to validate gas distribution maps produced by autonomous mobile robots. Previous ground truth measurements of gas dispersion have been mostly based on expensive tracer optical methods or 2D chemical sensor grids deployed only at ground level. With the ever-increasing trend towards gas-sensitive aerial robots, 3D measurements of gas dispersion become necessary to characterize the environment these platforms can explore. This paper presents ten different experiments performed with a 3D grid of 27 metal oxide semiconductor (MOX) sensors to visualize the temporal evolution of gas distribution produced by an evaporating ethanol source placed at different locations in an office room, including variations in height, release rate and air flow. We also studied which features of the MOX sensor signals are optimal for predicting the source location, considering different lengths of the measurement window. We found strongly time-varying and counter-intuitive gas distribution patterns that disprove some assumptions commonly held in the MRO field, such as that heavy gases disperse along ground level. Correspondingly, ground-level gas distributions were rarely useful for localizing the gas source and elevated measurements were much more informative. We make the dataset and the code publicly available to enable the community to develop, validate, and compare new approaches related to gas sensing in complex environments.

JTD Keywords: Mobile robotic olfaction, Metal oxide gas sensors, Signal processing, Sensor networks, Gas source localization, Gas distribution mapping

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on-demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self-propelled MNMs for on-demand biomedical cargo transportation, including their self-propulsion mechanisms, guidance strategies, as well as proof-of-concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.

JTD Keywords: Biomedical applications, Cargo transportation, Guidance strategies, Micro/nanomotors, Self-propulsion

Rice is a staple food of more than half of the world’s population; more than 3.5 billion inhabitants depend on rice for obtaining 20% of their daily calorie intake. Nitrogen is the most important for crop growth and yield potential. Indeed, nitrogen is essential to stimulate tillering, leaf growth, photosynthesis, and protein synthesis. Significant achievements have recently been observed at the molecular level in nitrogen use efficiency and water use efficiency in plants. In this chapter we will discuss the following issue: (i) definition of both nitrogen use efficiency and water use efficiency, (ii) genes responsible for nitrogen use efficiency and water use efficiency, (iii) best ways for improving water and nutrient use efficiency in rice, and (iv) optimizing nitrogen options for improving water and nitrogen use efficiency of rice under different water regimes.

JTD Keywords: Rice, Water use efficiency, Nitrogen use efficiency, Breeding, Genomics approaches

The coexistence between species that occurs in some infections remains hard to achieve in vitro since bacterial fitness differences eventually lead to a single organism dominating the mixed culture. Pseudomonas aeruginosa and Staphylococcus aureus are major pathogens found growing together in biofilms in disease-affected lungs or wounds. Herein, we tested and analyzed different culture media, additives and environmental conditions to support P. aeruginosa and S. aureus coexistence in vitro. We have unraveled the potential of DMEM to support the growth of these two organisms in mature cocultured biofilms (three days old) in an environment that dampens the pH rise. Our conditions use equal initial inoculation ratios of both strains and allow the stable formation of separate S. aureus microcolonies that grow embedded in a P. aeruginosa biofilm, as well as S. aureus biofilm overgrowth when bovine serum albumin is added to the system. Remarkably, we also found that S. aureus survival is strictly dependent on a well-characterized phenomenon of oxygen stratification present in the coculture biofilm. An analysis of differential tolerance to gentamicin and ciprofloxacin treatment, depending on whether P. aeruginosa and S. aureus were growing in mono- or coculture biofilms, was used to validate our in vitro coculture conditions.

JTD Keywords: Applied microbiology, Biofilms

This paper describes the development and validation of the currently smallest aerial platform with olfaction capabilities. The developed Smelling Nano Aerial Vehicle (SNAV) is based on a lightweight commercial nano-quadcopter (27 g) equipped with a custom gas sensing board that can host up to two in situ metal oxide semiconductor (MOX) gas sensors. Due to its small form-factor, the SNAV is not a hazard for humans, enabling its use in public areas or inside buildings. It can autonomously carry out gas sensing missions of hazardous environments inaccessible to terrestrial robots and bigger drones, for example searching for victims and hazardous gas leaks inside pockets that form within the wreckage of collapsed buildings in the aftermath of an earthquake or explosion. The first contribution of this work is assessing the impact of the nano-propellers on the MOX sensor signals at different distances to a gas source. A second contribution is adapting the ‘bout’ detection algorithm, proposed by Schmuker et al. (2016) to extract specific features from the derivative of the MOX sensor response, for real-time operation. The third and main contribution is the experimental validation of the SNAV for gas source localization (GSL) and mapping in a large indoor environment (160 m2) with a gas source placed in challenging positions for the drone, for example hidden in the ceiling of the room or inside a power outlet box. Two GSL strategies are compared, one based on the instantaneous gas sensor response and the other one based on the bout frequency. From the measurements collected (in motion) along a predefined sweeping path we built (in less than 3 min) a 3D map of the gas distribution and identified the most likely source location. Using the bout frequency yielded on average a higher localization accuracy than using the instantaneous gas sensor response (1.38 m versus 2.05 m error), however accurate tuning of an additional parameter (the noise threshold) is required in the former case. The main conclusion of this paper is that a nano-drone has the potential to perform gas sensing tasks in complex environments.

JTD Keywords: Robotics, Signal processing, Electronics, Gas source localization, Gas distribution mapping, Gas sensors, Drone, UAV, MOX sensor, Quadcopter

Introduction: The role of lung mesenchymal stem cells (L-MSCs) in pulmonary diseases remain to be fully elucidated. A relevant open question is to understand the crosstalk between L-MSCs and lung extracellular matrix (L-ECM). To this end, a suitable 3D model including MSCs and L-ECM is of high interest. Aim: To study how L-MSCs can be 3D bioprinted, cultured and harvested from L-ECM hydrogels. Methods: L-MSCs were isolated from Sprague-Dawley rats following established protocols. Porcine lungs were decellularized by a detergent-based procedure. The resulting L-ECM was freeze-dried, milled in liquid nitrogen and enzymatically digested by pepsin. After pH neutralization, resulting pre-gels were mixed with L-MSCs and 3D bioprinted by using F-127 as structural and sacrificial hydrogel. Cells were harvested from the 3D hydrogel by digestion with collagenase after 7 days of 3D culture and reseeded in standard plastic 2D culture plates. Cell viability and spatial distribution within the hydrogel was evaluated by live/dead (Thermo Scientific, MA, USA) staining and laser scanning confocal imaging. Biological activity was evaluated by hydrogel contraction assays. Results: Viability higher than 90% and homogenous 3D spatial distribution of L-MSCs were observed. Cells contracted the hydrogel up to 75% of their original size, showing that L-MSCs had an active interaction with the L-ECM. Recovered L-MSCs from the bioprinted structures were able to spread and proliferate when reseeded in plastic. Conclusion: Cell-laden hydrogels based on L-ECM can be used as bioink to build realistic 3D models for studying cell-matrix crosstalk in respiratory diseases.

JTD Keywords: Lung mechanics, Experimental approaches

Emerging nanobiotechnologies can offer solutions to the current and future challenges in medicine. By covering topics from regenerative medicine, tissue engineering, drug delivery, bionanofabrication, and molecular biorecognition, this Special Issue aims to provide an update on the trends in nanomedicine and drug delivery using biomimetic approaches, and the development of novel biologically inspired devices for the safe and effective diagnosis, prevention, and treatment of disease.

JTD Keywords: Bioinspired nanotechnologies, Bionanofabrication, Bio-nano measurement and microscopy, Nanomaterials for biological and medical applications, Nanoassemblies, Nanostructured surfaces, Drug delivery, Nanobioelectronics, Integrated systems/nanobiosensors, Nanotoxicology, Graphene-based applications

Gas distribution modelling can provide potentially life-saving information when assessing the hazards of gaseous emissions and for localization of explosives, toxic or flammable chemicals. In this work, we deployed a three-dimensional (3D) grid of metal oxide semiconductor (MOX) gas sensors deployed in an office room, which allows for novel insights about the complex patterns of indoor gas dispersal. 12 independent experiments were carried out to better understand dispersion patters of a single gas source placed at different locations of the room, including variations in height, release rate and air flow profiles. This dataset is denser and richer than what is currently available, i.e., 2D datasets in wind tunnels. We make it publicly available to enable the community to develop, validate, and compare new approaches related to gas sensing in complex environments.

JTD Keywords: MOX, Metal oxide, Flow visualization, Gas sensors, Gas distribution mapping, Sensor grid, 3D, Gas source localization, Indoor

This chapter takes the view that emotions of living machines can be seen from the perspective of self-regulation and appraisal. We will first look at the pragmatic needs to endow machines with emotions and subsequently describe some of the historical background of the science of emotions and its different interpretations and links to affective neuroscience. Subsequently, we argue that emotions can be cast in terms of self-regulation where they provide for a descriptor of the state of the homeostatic processes that maintain the relationship between the agent and its internal and external environment. We augment the notion of homeostasis with that of allostasis which signifies a change from stability through a fixed equilibrium to stability through continuous change. The chapter shows how this view can be used to create complex living machines where emotions are anchored in the need fulfillment of the agent, in this case considering both utilitarian and epistemic needs.

JTD Keywords: Emotion, Motivation, Needs, Appraisal, Self-regulation, Homeostasis, Allostasis, Human–robot interaction, James–Lange theory

In the field of micromotors many efforts are taken to find a substitute for peroxide as fuel. While most approaches turn towards other toxic high energy chemicals such as hydrazine, we introduce an energy source that is widely used in nature: light. Light is an ideal source of energy and some materials, such as AgCl, have the inherent property to transform light energy for chemical processes, which can be used to achieve propulsion. In the case of silver chloride, one observed process after light exposure is surface modification which leads to the release of ions generating chemo-osmotic gradients. Here we present endeavours to use those processes to propel uniquely shaped micro objects of micro star morphology with a high surface to volume ratio, study their dynamics and present approaches to go towards real environmental applications.

JTD Keywords: Self-propellers, Silver chloride, Environmental applications, Photoactive colloids, Anti bacterial

Introduction: Continuous positive airway pressure (CPAP) is the first-choice treatment for obstructive sleep apnoea (OSA), but adherence is frequently suboptimal. Innovative, patient-centred interventions are, therefore, needed to enhance compliance. Due to its low cost and ubiquity, mobile health (mHealth) technology seems particularly suited for this purpose. We endeavoured to develop an mHealth application called “APPnea,” aimed at promoting patient self-monitoring of CPAP treatment. We then assessed the feasibility and acceptability of APPnea in a group of OSA patients. Methods: Consecutive OSA patients used APPnea for six weeks. APPnea gave patients daily reminders to answer three questions about their OSA treatment (CPAP use, physical activity, and diet) and prompted them to upload their body weight weekly. Answers were saved to a secure server for further analysis. After completing the study, patients gave their anonymous opinions about APPnea. Results: We enrolled 60 patients with OSA receiving CPAP treatment. The mean age was 56 ± 10 years and the apnoea–hypopnea index was 47 ± 25 events/hour. In total, 63% of participants completed the daily questionnaire for more than 66% of the study period. Objective CPAP compliance was generally high (5.3 ± 1.6 hours/night). In a subset of 38 patients naïve to CPAP, those who used APPnea regularly had significantly higher CPAP compliance. Satisfaction levels were high for the majority of users. Conclusion: This mHealth intervention is not only feasible but also satisfactory to patients. Although larger randomized trials and cost-effectiveness studies should be performed, this study shows that APPnea could promote participation and improve compliance among patients with OSA, thereby improving outcomes.

JTD Keywords: CPAP, MHealth, Sleep apnoea, Smartphone application

Background: Most stroke survivors continue to experience motor impairments even after hospital discharge. Virtual reality-based techniques have shown potential for rehabilitative training of these motor impairments. Here we assess the impact of at-home VR-based motor training on functional motor recovery, corticospinal excitability and cortical reorganization. Objective: The aim of this study was to identify the effects of home-based VR-based motor rehabilitation on (1) cortical reorganization, (2) corticospinal tract, and (3) functional recovery after stroke in comparison to home-based occupational therapy. Methods: We conducted a parallel-group, controlled trial to compare the effectiveness of domiciliary VR-based therapy with occupational therapy in inducing motor recovery of the upper extremities. A total of 35 participants with chronic stroke underwent 3 weeks of home-based treatment. A group of subjects was trained using a VR-based system for motor rehabilitation, while the control group followed a conventional therapy. Motor function was evaluated at baseline, after the intervention, and at 12-weeks follow-up. In a subgroup of subjects, we used Navigated Brain Stimulation (NBS) procedures to measure the effect of the interventions on corticospinal excitability and cortical reorganization. Results: Results from the system?s recordings and clinical evaluation showed significantly greater functional recovery for the experimental group when compared with the control group (1.53, SD 2.4 in Chedoke Arm and Hand Activity Inventory). However, functional improvements did not reach clinical significance. After the therapy, physiological measures obtained from a subgroup of subjects revealed an increased corticospinal excitability for distal muscles driven by the pathological hemisphere, that is, abductor pollicis brevis. We also observed a displacement of the centroid of the cortical map for each tested muscle in the damaged hemisphere, which strongly correlated with improvements in clinical scales. Conclusions: These findings suggest that, in chronic stages, remote delivery of customized VR-based motor training promotes functional gains that are accompanied by neuroplastic changes. Trial Registration: International Standard Randomized Controlled Trial Number NCT02699398 (Archived by ClinicalTrials.gov at https://clinicaltrials.gov/ct2/show/NCT02699398?term=NCT02699398&rank=1)

JTD Keywords: Stroke, Movement disorder, Recovery of function, neuroplasticity, Transcranial magnetic stimulation, Physical therapy, Hemiparesis, Computer applications software

Surface-conductive Janus spherical motors are fabricated by wrapping silica particles with reduced graphene oxide capped with a thin Pt layer. These motors exhibit a 100% enhanced velocity as compared to standard SiO2–Pt motors. Furthermore, the versatility of graphene may open up possibilities for a diverse range of applications from active drug delivery systems to water remediation.

JTD Keywords: Enhanced speed, Graphene wrapping, Janus micromotors, Janus particles, Micromotors, Surface conduction

In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources.

JTD Keywords: Environmental monitoring, Gas discrimination, Gas distribution mapping, Service robots, Open sampling systems, PID, Metal oxide sensors

Poly(vinylchloride) (PVC) is the most common polymer matrix used in the fabrication of ion-selective electrodes (ISEs). However, the surfaces of PVC-based sensors have been reported to show membrane instability. In an attempt to overcome this limitation, here we developed two alternative methods for the preparation of highly stable and robust ion-selective sensors. These platforms are based on the selective electropolymerization of poly(3,4-ethylenedioxythiophene) (PEDOT), where the sulfur atoms contained in the polymer covalently interact with the gold electrode, also permitting controlled selective attachment on a miniaturized electrode in an array format. This platform sensor was improved with the crosslinking of the membrane compounds with poly(ethyleneglycol) diglycidyl ether (PEG), thus also increasing the biocompatibility of the sensor. The resulting ISE membranes showed faster signal stabilization of the sensor response compared with that of the PVC matrix and also better reproducibility and stability, thus making these platforms highly suitable candidates for the manufacture of robust implantable sensors.

JTD Keywords: Biomedicine, Electrochemistry, Endoscope, Implantable device, Ion-selective electrode (ISE) sensor, Ischemia, pH detection, Biocompatibility, Chemical sensors, Electrochemistry, Electrodes, Electropolymerization, Endoscopy, Functional polymers, Implants (surgical), Ion selective electrodes, Medical applications, Polyvinyl chlorides, Stabilization, Biomedical applications, Biomedicine, Implantable devices, Ion selective sensors, Ischemia, Membrane instability, pH detection, Poly(3 ,4 ethylenedioxythiophene) (PEDOT), Ion selective membranes

This article reports on the research and development of a cutting-edge biomedical device for continuous in-vivo glucose monitoring. This entirely public-funded process of technological innovation has been conducted at the University of Barcelona within a context of converging technologies involving the fields of medicine, physics, chemistry, biology, telecommunications, electronics and energy. The authors examine the value chain and the market challenges faced by in-vivo implantable biomedical devices based on nanotechnologies. In so doing, they trace the process from the point of applied research to the final integration and commercialization of the product, when the social rate of return from academic research can be estimated. Using a case-study approach, the paper also examines the high-tech activities involved in the development of this nano-enabled device and describes the technology and innovation management process within the value chain conducted in a University-Hospital-Industry-Administration-Citizens framework. Here, nanotechnology is seen to represent a new industrial revolution, boosting the biomedical devices market. Nanosensors may well provide the tools required for investigating biological processes at the cellular level in vivo when embedded into medical devices of small dimensions, using biocompatible materials, and requiring reliable and targeted biosensors, high speed data transfer, safely stored data, and even energy autonomy.

JTD Keywords: Biomedical device, Diabetes, Innovation management, Nanobiosensor, Nanotechnology, Research commercialization, Technology transfer, Academic research, Applied research, Barcelona, Biocompatible materials, Biological process, Biomedical analysis, Biomedical devices, Cellular levels, Converging technologies, Glucose monitoring, High-speed data transfer, Implantable biomedical devices, Implantable devices, In-vivo, Industrial revolutions, Innovation management, Medical Devices, Nanobiosensor, Rate of return, Research and development, Technological innovation, Value chains, Biological materials, Biomedical engineering, Biosensors, Commerce, Data transfer, Earnings, Engineering education, Glucose, Implants (surgical), Industrial research, Innovation, Medical problems, Nanosensors, Nanotechnology, Technology transfer, Equipment

In this study, polylactic acid (PLA) and polyethylene glycol (PEG) were combined with soluble CaP glass particles and processed by rapid prototyping to obtain fully biodegradable structures for Tissue Engineering applications. The obtained 3D biodegradable structures were characterized in terms of their architecture and mechanical properties. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using Scanning Electron Microscopy (SEM), micro-computed tomography (micro-CT) and mechanical testing, respectively. Well defined structures with pore size of 350-400μm (in the axial view), struts width of approximately 70-80μm, and a porosity ranging between 60-65% were obtained. The combination RP and PLA/PEG/CaP glass turned into promising fully degradable, mechanically stable, bioactive and biocompatible composite scaffolds for TE.

JTD Keywords: Axial view, Biodegradable composites, Composite scaffolds, Glass particles, Mechanically stable, Micro architectures, Micro computed tomography (micro-CT), Poly lactic acid, Scaffold morphology, Tissue engineering applications, Well-defined structures, Bioactive glass, Mechanical properties, Mechanical testing, Polyethylene glycols, Polymer blends, Rapid prototyping, Scaffolds (biology), Scanning electron microscopy, Computerized tomography

This paper reviews commonly used methods of analyzing and interpreting friction, adhesion and nanoindentation with an AFM tip test data, with a particular emphasis of the testing of single crystals, metals, ceramics and ceramic coatings. Experimental results are reported on the friction, mechanical and adhesion properties of these materials. The popularity of AFM testing is evidenced by the large quantity of papers that report such measurements in the last decade. Unfortunately, a lot of information about these topics is scare in the literature. The present paper is aimed to present the basic physical modelling employed and also some examples using each technique.

JTD Keywords: Mechanical properties, Plasticity, Biomedical applications, Engine components

Analyzing the pore-size distribution of porous materials, made up of an aggregation of interconnected pores, is a demanding task. Mercury intrusion porosimetry (MIP) is a physical method that intrudes mercury into a sample at increasing pressures to obtain a pore-size histogram. This method has been simulated in-silice with several approaches requiring prior computation of a skeleton. We present a new approach to simulate MIP that does not require skeleton computation. Our method is an iterative process that considers the diameters corresponding to pressures. At each iteration, geometric tests detect throats for the corresponding diameter and a CCL process collects the region invaded by the mercury. Additionally, a new decomposition model called CUDB, is used. This is suitable for computing the throats and performs better with the CCL algorithm than a voxel model. Our approach obtains the pore-size distribution of the porous medium, and the corresponding pore graph.

JTD Keywords: Micro CT, Pore map, Porous media, Skeleton, Virtual MIP

This paper presents a first approach on multi-pathogen detection system for portable point-of-care applications on discrete electronics field. The main interest is focused on the development of custom built electronic solutions for bioelectronics applications, from discrete devices to ASICS solutions.

JTD Keywords: Application specific integrated circuits, Biomedical electronics, Biosensors

In this work a calcium phosphate (CPC)/polymer blend was developed with the advantage of being moldable and capable of in situ setting to form calcium deficient hydroxyapatite under physiological conditions in an aqueous environment at body temperature. The CPC paste consists in a mix of R cement, glycerol as a liquid phase carrier and a biodegradable hydrogel such as Polyvinyl alcohol, which acts as a binder. Microstructure and mechanical analysis shows that the CPC blend can be used as an injectable implant for low loaded applications and fast adsorption requirements. The storage for commercial distribution was also evaluated and the properties of the materials obtained do not significantly change during storage at -18A degrees C.

JTD Keywords: Clinical-applications, Composites, Regeneration, Behavior, Scaffold, Repair

A new method for the quantification of amplitude variations in biomedical signals through moving approximate entropy is presented. Unlike the usual method to calculate the approximate entropy (ApEn), in which the tolerance value (r) varies based on the standard deviation of each moving window, in this work ApEn has been computed using a fixed value of r. We called this method, moving approximate entropy with fixed tolerance values: ApEn/sub f/. The obtained results indicate that ApEn/sub f/ allows determining amplitude variations in biomedical data series. These amplitude variations are better determined when intermediate values of tolerance are used. The study performed in diaphragmatic mechanomyographic signals shows that the ApEn/sub f/ curve is more correlated with the respiratory effort than the standard RMS amplitude parameter. Furthermore, it has been observed that the ApEn/sub f/ parameter is less affected by the existence of impulsive, sinusoidal, constant and Gaussian noises in comparison with the RMS amplitude parameter.

JTD Keywords: Practical, Theoretical or Mathematical/ biomechanics, Entropy, Gaussian noise, Medical signal processing, Muscle, Random processes/ approximate entropy interpretation, Fixed tolerance values, Diaphragmatic mechanomyographic signals, ApEnf curve, Respiratory effort, Gaussian noises

The design of orthotic devices that tries to fit to the anthropomorphic structure of human limbs faces the problem of achieving the highest approximation to the anatomical kinematics. This paper studies the main characteristics and performances of orthotic devices, mainly focusing on the upper limbs, and proposes a solution to the problem of the superposition of rotation and displacement of some joints, as the shoulder, elbow or knee. A 3 DoF virtual joint is proposed to emulate a human joint, solving the isocentricity and size adaptation of most current orthosis.

JTD Keywords: Prosthetics and other practical applications, Prosthetics and orthotics, Prosthetic and orthotic control systems, Robotics, Biomechanics (mechanical engineering), Robot and manipulator mechanics

The main goal of this work is to propose a haptics guideline in human-robot systems focused on the relationship between the human and robot task, the use of a physical interface and the object to manipulate. With this aim, this guideline presents two main parts: a set of heuristic indicators and a qualitative evaluation. In order to assess its ergonomic validation, an application over a well known haptics interface is presented. The final goal of this work is the study of possible applications in regular laboratory conditions in order to improve the design and use of human-robot haptic interfaces in telerobotics applications.

JTD Keywords: Haptic interface design, Human-robot interaction, Surgical applications, Teleoperation

BACKGROUND:Ribonucleotide reductases (RNRs) catalyse the only known de novo pathway for deoxyribonucleotide synthesis, and are therefore essential to DNA-based life. While ribonucleotide reduction has a single evolutionary origin, significant differences between RNRs nevertheless exist, notably in cofactor requirements, subunit composition and allosteric regulation. These differences result in distinct operational constraints (anaerobicity, iron/oxygen dependence and cobalamin dependence), and form the basis for the classification of RNRs into three classes.DESCRIPTION:In RNRdb (Ribonucleotide Reductase database), we have collated and curated all known RNR protein sequences with the aim of providing a resource for exploration of RNR diversity and distribution. By comparing expert manual annotations with annotations stored in Genbank, we find that significant inaccuracies exist in larger databases. To our surprise, only 23% of protein sequences included in RNRdb are correctly annotated across the key attributes of class, role and function, with 17% being incorrectly annotated across all three categories. This illustrates the utility of specialist databases for applications where a high degree of annotation accuracy may be important. The database houses information on annotation, distribution and diversity of RNRs, and links to solved RNR structures, and can be searched through a BLAST interface. RNRdb is accessible through a public web interface at http://rnrdb.molbio.su.se.CONCLUSION:RNRdb is a specialist database that provides a reliable annotation and classification resource for RNR proteins, as well as a tool to explore distribution patterns of RNR classes. The recent expansion in available genome sequence data have provided us with a picture of RNR distribution that is more complex than believed only a few years ago; our database indicates that RNRs of all three classes are found across all three cellular domains. Moreover, we find a number of organisms that encode all three classes.

JTD Keywords: Enzymology (Biochemistry and Molecular Biophysics), Computer Applications (Computational Biology)

Continuous advances on diagnostic techniques based on medical images, as well as the incorporation of new techniques in surgical instruments are progressively changing the new surgical procedures. Also, new minimally invasive techniques, which are currently highly consolidated, have produced significant advances, both from the technological and from the surgical treatment perspectives. The limitations that the manual realization of surgical interventions implies, in what refers to precision and accessibility, can be tackled with the help of robotics. In the same way, sensor based robot control techniques are opening new possibilities for the introduction of more improvements in these procedures, either relying on teleoperation, in which the surgeon and the robot establish their best synergy to get the optimal results, or by means of the automation of some specific actions or tasks. In this article the effect of robotics in the evolution of surgical techniques is described. Starting with a review of the robotics application fields, the article continues analyzing the methods and technologies involved in the process of robotizing surgical procedures, as well as the surgeon-robot interaction systems.

JTD Keywords: Robotics, Medical Applications, Teleoperation, Biomedical Systems, Computer Aided Surgery, Human-Machine Interaction

With the goal of deepen in the understanding of coding of chemical information in the olfactory system, a large data set consisting of rat's olfactory bulb activity values in response to several different volatile compounds has been analyzed by fuzzy c-means clustering methods. Clustering should help to discover groups of glomeruli that are similary activated according to their response profiles across the odorants. To investigate the significance of the achieved fuzzy partitions we developed and applied a novel validity approach based on cluster stability. Our results show certain level of glomerular clustering in the olfactory bulb and indicate that exist a main chemo-topic subdivision of the glomerular layer in few macro-area which are rather specific to particular functional groups of the volatile molecules.

JTD Keywords: Olfactory bulb, 2-deoxyglucose mapping, Olfactory coding, Cluster analysis, Cluster validity

The authors are working toward the design of a device for the detection of oxygen, following a discrete and an integrated instrumentation implementation. The discrete electronics are also used for preliminary analysis, to confirm the validity of the conception of system, and its set-up would be used in the characterization of the integrated device, waiting for the chip fabrication. This paper presents the design of a small and portable potentiostat integrated with electrodes, which is cheap and miniaturized, which can be applied for on-site measurements for the simultaneous detection of O/sub 2/ and temperature in water systems. As a first approach a discrete PCB has been designed based on commercial discrete electronics and specific oxygen sensors. Dissolved oxygen concentration (DO) is an important index of water quality and the ability to measure the oxygen concentration and temperature at different positions and depths would be an important attribute to environmental analysis. Especially, the objective is that the sensor and the electronics can be integrated in a single encapsulated device able to be submerged in environmental water systems and be able to make multiple measurements. For our proposed application a small and portable device is developed, where electronics and sensors are miniaturized and placed in close proximity to each other. This system would be based on the sensors and electronics, forming one module, and connected to a portable notebook to save and analyze the measurements on-line. The key electronics is defined by the potentiostat amplifier, used to fix the voltage between the working (WE) and reference (RE) electrodes following an input voltage (Vin). Vin is a triangular signal, programmed by a LabView/sup c / interface, which is also used to represent the CV transfers. To obtain a smaller and compact solution the potentiostat amplifier has also been integrated defining a full custom ASIC amplifier, which is in progress, looking for a point-of-care device. These circuits have been designed with a 0.13 mu m technology from ST Microelectronics through the CMP-TIMA service.

JTD Keywords: Amplifiers, Application specific integrated circuits, Chemical sensors, Electrodes, Portable instruments, Temperature measurement, Water sources

This 167-page book is volume 188 in the series 'Studies in computational intelligence.' This volume contain 9 extensive chapters written in English. This volume presents a collection of research advances in biologically inspired signal processing for chemical sensing. The olfactory system, and the gustatory system to a minor extent, has been taken in the last decades as a source of inspiration to develop artificial sensing systems. The recognition of odors by the olfactory system entails a number of signal processing functions such as preprocessing, dimensionality reduction, contrast enhancement, and classification. Using mathematical models to mimic the architecture of the olfactory system, these processing functions can be applied to chemical sensor signals. This book provides background on the olfactory system including a review on information processing in the insect olfactory system along with a proposed signal processing architecture based on the mammalian cortex. It also provides some bio-inspired approaches to process chemical sensor signals such as an olfactory mucosa to improve odor separation and a model of olfactory receptor neuron convergence to correlated sensor responses to an odor and his organoleptic properties. This book will useful to those working or studying in the areas of sensory reception and computational biology.

JTD Keywords: Nervous System (Neural Coordination), Computer Applications (Computational Biology), Sense Organs (Sensory Reception)

Polymers with high glass transition temperatures, fluorinated ethylene propylene copolymer (FEP) and poly(ethylene naphthalate) (PEN), have been used in imprint lithography as a protective support layer and as a secondary mould, to imprint superficial structures into a polymer with a lower glass transition temperature, namely poly(methyl methacrylate) (PMMA). As a support layer, FEP replaces fragile silicon based supports for the production of freestanding, structured sheets of PMMA, useful, for example, in biomedical applications where transmittance optical microscopy is required. Secondary PEN moulds, produced by imprinting using silicon-based primary moulds, have been used to transfer sub-micrometer tall structures to a freestanding PMMA sheet. Similarly, hole structures, with different dimensions, have been embossed in both sides of a PMMA sheet simultaneously.

JTD Keywords: Polymer engineering, Embossing, Nanoimprint lithography, Biomedical applications