3D-printed biosensors in biomedical applications exploiting plasmonic phenomena and antibody self-assembled monolayers.

In this work, a 3D-printed plasmonic chip based on a silver-gold bilayer was developed in order to enhance the optical response of the surface plasmon resonance (SPR) probe. More specifically, numerical and experimental results were obtained on the 3D-printed SPR platform based on a silver-gold bilayer. Then, the optimized probe's gold plasmonic interface was functionalized with a specific antibody directed against the p27Kip1 protein (p27), an important cell cycle regulator. The 3D-printed plasmonic biosensor was tested for p27 detection with good selectivity and a detection limit of 55 pM. The biosensor system demonstrated performance similar to commercially available ELISA (enzyme-linked immunoassay) kits, with several advantages, such as a wide detection range and a modular and simple-based architecture. The proposed biosensing technology offers flexible deployment options that are useful in disposable, low-cost, small-size, and simple-to-use biochips, envisaging future applications in experimental and biomedical research.

Epoxy-Based Blend Formulation for Dual Curing in Liquid Crystal Display 3D Printing: A Study on Thermomechanical Properties Variation for Enhanced Printability.

The aim of this study was to explore the thermal properties of epoxy-acrylate blends for the liquid crystal display (LCD) 3D printing technique. Starting from an epoxy-acrylate blend with a ratio of epoxy to acrylate of 50:50, the effect of adding a reactive monofunctional epoxy diluent was evaluated. The diluent was a resin composed by oxirane, mono[(C12-14 alkyl) methyl] derivatives selected for its low viscosity (i.e., 1.8 Poise) at room temperature and its reactivity. The diluent content varied from 15 to 25 wt% and, for all the formulation, double curing cycles, where thermal curing followed photocuring, were studied. The effect of different curing temperatures was also evaluated. The control of the diluent content and of the curing temperature allowed tailoring of the thermomechanical resin properties while improving the resin's processability. The glass transition ranged from 115.4 °C to 90.8 °C depending on the combination of diluent content and post-curing temperature. The resin developed displayed a faster processing time tested on a reference part with printing time of 4 h and 20 min that was much lower than the printing times (7 and 16 h) observed for the starting formulations.

Projection Micro-Stereolithography to Manufacture a Biocompatible Micro-Optofluidic Device for Cell Concentration Monitoring.

In this work, a 3D printed biocompatible micro-optofluidic (MoF) device for two-phase flow monitoring is presented. Both an air-water bi-phase flow and a two-phase mixture composed of micrometric cells suspended on a liquid solution were successfully controlled and monitored through its use. To manufacture the MoF device, a highly innovative microprecision 3D printing technique was used named Projection Microstereolithography (PµSL) in combination with the use of a novel 3D printable photocurable resin suitable for biological and biomedical applications. The concentration monitoring of biological fluids relies on the absorption phenomenon. More precisely, the nature of the transmission of the light strictly depends on the cell concentration: the higher the cell concentration, the lower the optical acquired signal. To achieve this, the microfluidic T-junction device was designed with two micrometric slots for the optical fibers' insertion, needed to acquire the light signal. In fact, both the micro-optical and the microfluidic components were integrated within the developed device. To assess the suitability of the selected biocompatible transparent resin for optical detection relying on the selected working principle (absorption phenomenon), a comparison between a two-phase flow process detected inside a previously fully characterized micro-optofluidic device made of a nonbiocompatible high-performance resin (HTL resin) and the same made of the biocompatible one (BIO resin) was carried out. In this way, it was possible to highlight the main differences between the two different resin grades, which were further justified with proper chemical analysis of the used resins and their hydrophilic/hydrophobic nature via static water contact angle measurements. A wide experimental campaign was performed for the biocompatible device manufactured through the PµSL technique in different operative conditions, i.e., different concentrations of eukaryotic yeast cells of Saccharomyces cerevisiae (with a diameter of 5 µm) suspended on a PBS (phosphate-buffered saline) solution. The performed analyses revealed that the selected photocurable transparent biocompatible resin for the manufactured device can be used for cell concentration monitoring by using ad hoc 3D printed micro-optofluidic devices. In fact, by means of an optical detection system and using the optimized operating conditions, i.e., the optimal values of the flow rate FR=0.1 mL/min and laser input power P∈{1,3} mW, we were able to discriminate between biological fluids with different concentrations of suspended cells with a robust working ability R2=0.9874 and Radj2=0.9811.

A 3D-Printed Micro-Optofluidic Chamber for Fluid Characterization and Microparticle Velocity Detection.

This work proposes a multi-objective polydimethylsiloxane (PDMS) micro-optofluidic (MoF) device suitably designed and manufactured through a 3D-printed-based master-slave approach. It exploits optical detection techniques to characterize immiscible fluids or microparticles in suspension inside a compartment specifically designed at the core of the device referred to as the MoF chamber. In addition, we show our novel, fast, and cost-effective methodology, dual-slit particle signal velocimetry (DPSV), for fluids and microparticle velocity detection. Different from the standard state-of-the-art approaches, the methodology focuses on signal processing rather than image processing. This alternative has several advantages, including the ability to circumvent the requirement of complex and extensive setups and cost reduction. Additionally, its rapid processing speed allows for real-time sample manipulations in ongoing image-based analyses. For our specific design, optical signals have been detected from the micro-optics components placed in two slots designed ad hoc in the device. To show the devices' multipurpose capabilities, the device has been tested with fluids of various colors and densities and the inclusion of synthetic microparticles. Additionally, several experiments have been conducted to prove the effectiveness of the DPSV approach in estimating microparticle velocities. A digital particle image velocimetry (DPIV)-based approach has been used as a baseline against which the outcomes of our methods have been evaluated. The combination of the suitability of the micro-optical components for integration, along with the MoF chamber device and the DPSV approach, demonstrates a proof of concept towards the challenge of real-time total-on-chip analysis.

Chemical Recycling of Fully Recyclable Bio-Epoxy Matrices and Reuse Strategies: A Cradle-to-Cradle Approach.

Currently, the epoxy resin market is expressing concerns about epoxy resins' non-recyclability, which can hinder their widespread use. Moreover, epoxy monomers are synthesized via petroleum-based raw materials, which also limits their use. So, it is crucial to find more environmentally friendly alternative solution for their formulation. Within this context, the aim of this paper is to exploit a Cradle-to-Cradle approach, which consists of remodeling and reshaping the productive cycle of consumer products to make sure that they can be infinitely reused rather than just being recycled with a downgrading of their properties or uses, according to the principle of the complete circular economy. Indeed, after starting with a fully-recyclable bio-based epoxy formulation and assessing its recyclability as having a process yield of 99%, we obtained a recycled polymer that could be reused, mixing with the same bio-based epoxy formulation with percentages varying from 15 wt% to 27 wt%. The formulation obtained was thoroughly characterized by a dynamic-mechanical analysis, differential scanning calorimetry, and flexural tests. This approach had two advantages: (1) it represented a sustainable disposal route for the epoxy resin, with nearly all the epoxy resin recovered, and (2) the obtained recycled polymer could be used as a green component of the primary bio-based epoxy matrix. In the end, by using replicated general factorial designs (as statistical tools) combined with a proper optimization process, after carrying out a complete thermo-mechanical characterization of the developed epoxy formulations, the right percentage of recycled polymer content was selected with the aim of identifying the most performing epoxy matrix formulation in terms of its thermo-mechanical properties.

A Regression Approach to Model Refractive Index Measurements of Novel 3D Printable Photocurable Resins for Micro-Optofluidic Applications.

In this work, a quadratic polynomial regression model was developed to aid practitioners in the determination of the refractive index value of transparent 3D printable photocurable resins usable for micro-optofluidic applications. The model was experimentally determined by correlating empirical optical transmission measurements (the dependent variable) to known refractive index values (the independent variable) of photocurable materials used in optics, thus obtaining a related regression equation. In detail, a novel, simple, and cost-effective experimental setup is proposed in this study for the first time for collecting the transmission measurements of smooth 3D printed samples (roughness ranging between 0.04 and 2 µm). The model was further used to determine the unknown refractive index value of novel photocurable resins applicable in vat photopolymerization (VP) 3D printing techniques for manufacturing micro-optofluidic (MoF) devices. In the end, this study proved how knowledge of this parameter allowed us to compare and interpret collected empirical optical data from microfluidic devices made of more traditional materials, i.e., Poly(dimethylsiloxane) (PDMS), up to novel 3D printable photocurable resins suitable for biological and biomedical applications. Thus, the developed model also provides a quick method to evaluate the suitability of novel 3D printable resins for MoF device fabrication within a well-defined range of refractive index values (1.56; 1.70).

Full Recycling and Re-Use of Bio-Based Epoxy Thermosets: Chemical and Thermomechanical Characterization of the Recycled Matrices.

High performances of thermosets deriving from their covalent intermolecular cross-link bonds result in their low recyclability hindering the full exploitation of a truly circular approach for cured thermosets. In this experimental work, the recyclability of a bio-based fully recyclable epoxy resin using a mild chemical recycling process was demonstrated. The recycled polymer obtained was fully characterized to ascertain its structure and properties. MALDI (Matrix-Assisted Laser Desorption/Ionization), GPC (Gel Permeation Chromatography) and NMR (Nuclear Magnetic Resonance) spectroscopy to determine the chemical structure of the recycled polymer were used. The thermomechanical properties of the cured virgin network and of the recycled product obtained were measured by DSC (Differential Scanning Calorimetry) and DMA (Dynamic Mechanical Analysis). Thermogravimetric analysis of the recycled polymer was also performed. The recycled polymer was transformed into a polyurethane by reacting it with an isocyanate. The synthetized polyurethane obtained therefrom was thoroughly characterized by thermogravimetric analysis. This approach proved the possibility to up-scale the recycled product making it available for novel applications exploiting its re-use.

3D Printing Manufacturing of Polydimethyl-Siloxane/Zinc Oxide Micro-Optofluidic Device for Two-Phase Flows Control.

Tailored ZnO surface functionalization was performed inside a polydimethyl-siloxane (PDMS) microchannel of a micro-optofluidic device (mofd) to modulate its surface hydrophobicity to develop a method for fine tuning the fluid dynamics inside a microchannel. The wetting behavior of the surface is of particular importance if two different phases are used for system operations. Therefore, the fluid dynamic behavior of two immiscible fluids, (i) air-water and (ii) air-glycerol/water in PDMS mofds and ZnO-PDMS mofds was investigated by using different experimental conditions. The results showed that air-glycerol/water fluid was always faster than air-water flow, despite the microchannel treatment: however, in the presence of ZnO microstructures, the velocity of the air-glycerol/water fluid decreased compared with that observed for the air-water fluid. This behavior was associated with the strong ability of glycerol to create an H-bond network with the exposed surface of the zinc oxide microparticles. The results presented in this paper allow an understanding of the role of ZnO functionalization, which allows control of the microfluidic two-phase flow using different liquids that undergo different chemical interactions with the surface chemical terminations of the microchannel. This chemical approach is proposed as a control strategy that is easily adaptable for any embedded micro-device.

Fully Recyclable Bio-Based Epoxy Formulations Using Epoxidized Precursors from Waste Flour: Thermal and Mechanical Characterization.

Organic wastes represent an increasing pollution problem due to the exponential growth of their presence in the waste stream. Among these, waste flour cannot be easily reused by transforming it into high-value-added products. Another major problem is represented by epoxy-based thermosets, which have wide use but also poor recyclability. The object of the present paper is, therefore, to analyze both of these problems and come up with innovative solutions. Indeed, we propose a completely new approach, aimed at reusing the organic waste flour, by converting it into high-value epoxy-based thermosets that could be fully recycled into a reusable plastic matrix when added to the waste epoxy-based thermosets. Throughout the research activity, the organic waste was transformed into an epoxidized prepolymer, which was then mixed with a bio-based monomer cured with a cleavable ammine. The latter reactant was based on Recyclamine™ by Connora Technologies, and in this paper, we demonstrate that this original approach could work with the synthetized epoxy prepolymers derived from the waste flour. The cured epoxies were fully characterized in terms of their thermal, rheological, and flexural properties. The results obtained showed optimal recyclability of the new resin developed.

Microstructured Surface Plasmon Resonance Sensor Based on Inkjet 3D Printing Using Photocurable Resins with Tailored Refractive Index.

In this work, a novel approach to realize a plasmonic sensor is presented. The proposed optical sensor device is designed, manufactured, and experimentally tested. Two photo-curable resins are used to 3D print a surface plasmon resonance (SPR) sensor. Both numerical and experimental analyses are presented in the paper. The numerical and experimental results confirm that the 3D printed SPR sensor presents performances, in term of figure of merit (FOM), very similar to other SPR sensors made using plastic optical fibers (POFs). For the 3D printed sensor, the measured FOM is 13.6 versus 13.4 for the SPR-POF configuration. The cost analysis shows that the 3D printed SPR sensor can be manufactured at low cost (∼15 €) that is competitive with traditional sensors. The approach presented here allows to realize an innovative SPR sensor showing low-cost, 3D-printing manufacturing free design and the feasibility to be integrated with other optical devices on the same plastic planar support, thus opening undisclosed future for the optical sensor systems.

Development, Optimization and Characterization of Eudraguard®-based Microparticles for Colon Delivery.

Development of pH-dependent systems for colon delivery of natural active ingredients is an attractive area of research in the field of nutraceutical products. This study was focused on Eudraguard® resins, that are methacrylate copolymers approved as "food grade" by European Commission and useful for the production of food supplements. In particular, Eudraguard® Biotic (EUG-B), characterized by a pH-dependent solubility and Eudraguard® Control (EUG-C), whose chemical properties support a prolonged release of the encapsulated compounds, were tested. To obtain EUG microparticles, different preparation techniques were tested, in order to optimize the preparation method and observe the effect upon drug encapsulation and specific colonic release. Unloaded microparticles were initially produced to evaluate the influence of polymer characteristics on the formulation process; subsequently microparticles loaded with quercetin (QUE) as a low solubility model drug were prepared. The characterization of microparticles in the solid-state (FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry) indicated that QUE was uniformly dispersed in a non-crystalline state in the polymeric network, without strong signs of chemical interactions. Finally, to assess the ability of EUG-C and EUG-B to control the drug release in the gastric environment, and to allow an increased release at a colonic level, suitable in vitro release tests were carried out by simulating the pH variations along the gastro-intestinal tract. Among the evaluated preparation methods, those in which an aqueous phase was not present, and in particular the emulsion-solvent evaporation method produced the best microparticle systems. The in vitro tests showed a limited drug release at a gastric level and a good specific colon release.

Optimization of ZnO Nanorods Growth on Polyetheresulfone Electrospun Mats to Promote Antibacterial Properties.

Zinc oxide (ZnO) nanorods grown by chemical bath deposition (CBD) on the surface of polyetheresulfone (PES) electrospun fibers confer antimicrobial properties to the obtained hybrid inorganic-polymeric PES/ZnO mats. In particular, a decrement of bacteria colony forming units (CFU) is observed for both negative (Escherichia coli) and positive (Staphylococcus aureus and Staphylococcus epidermidis) Grams. Since antimicrobial action is strictly related to the quantity of ZnO present on surface, a CBD process optimization is performed to achieve the best results in terms of coverage uniformity and reproducibility. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) provide morphological and compositional analysis of PES/ZnO mats while thermogravimetric analysis (TGA) is useful to assess the best process conditions to guarantee the higher amount of ZnO with respect to PES scaffold. Biocidal action is associated to Zn2+ ion leaching in solution, easily indicated by UV-Vis measurement of metallation of free porphyrin layers deposited on glass.

Interlaminar Toughening of Epoxy Carbon Fiber Reinforced Laminates: Soluble Versus Non-Soluble Veils.

This work describes the evaluation of different interlaminar veils to improve the toughening of epoxy/carbon fiber composites manufactured by resin infusion. Three commercial veils have been used in the study: two electro spun thermoplastic nanofiber (Xantulayr® from Revolution Fibres) with different areal weight, and one micro carbon fibers veil (Optiveil® from TFP). Two laboratory made veils were also manufactured by electrospinning commercial polyethersulfone (PES) tougheners (Virantage by Solvay). The veils were selected to be either soluble or non-soluble in the epoxy resin matrix during curing. The solubility was analyzed by scanning electron microscopy and dynamic mechanical analysis testing on the cured laminates. The fracture energy was evaluated by double cantilever bending (DCB) testing under Mode I loading. The insoluble thermoplastic nanofibers showed the highest toughening efficiency, followed by the soluble nanofiber veils. The carbon fiber based veil showed no toughness improvement.