Advancements in Biomedical Applications of Calcium Phosphate Glass and Glass-Based Devices-A Review.

Calcium phosphate (CaP) glass has recently gained popularity as a promising material for a wide range of biomedical applications. Recent developments have seen CaP glasses moving from a passive implant material to an active degradable material, particularly as a major constituent of bioresorbable photonic devices. This holds great promise in advanced biomedical applications, since the main constituents of CaP glasses are present in the human body. In this review, the progressive advancements in the biomedical applications of calcium phosphate glass-based devices over the past 50 years are discussed. An overview of their role as reinforcing agents and the studies on doping their matrices for ion releasing and drug and gene delivery are reviewed. Recent applications of CaP glass and fibers in soft-tissue engineering and their potential for optical quality bioresorbable devices are then discussed along with the current challenges and potential future directions, emphasizing the promising role of CaP glass in the next generation of biomaterials. Considering their progress and potential in performing several biomedical functionalities over time, CaP glass-based devices hold promise for becoming enabling tools as an implantable, bioresorbable, multifunctional class of devices in future biomedicine.

Effect of Low Copper Doping on the Optical, Cytocompatible, Antibacterial, and SARS-CoV-2 Trapping Properties of Calcium Phosphate Glasses.

Calcium phosphate glasses (CPGs) are acquiring great importance in the biomedical field because of their thermomechanical and bioresorbable properties. In this study, optically transparent copper (1 mol %)-doped calcium phosphate glasses (CPGs_Cu) were prepared through the melt-quenching method, and their biocompatibility and antibacterial and antiviral properties were evaluated and compared with undoped CPGs. Biocompatibility was evaluated on murine fibroblast NIH-3T3 cells as a preliminary study of cytocompatibility. The in vitro tests were performed through indirect and direct cytotoxicity analyses by MTT and Alamar Blue assays and supported by electron microscopy observations. Microbiological analyses were performed against the most common Gram-negative and Gram-positive pathogens that cause nosocomial infections: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and the methicillin-resistant Staphylococcus aureus strain. In addition, the bioglass samples were exposed to SARS-CoV-2 to assess their effects on viral survival. The obtained results assessed the biocompatibility of both bioglass types and their ability to reduce the viral load and trap the virus. In addition, Cu2+-doped bioglass was found to be antibacterial despite its low content (1 mol %) of copper, making this a promising candidate material for biomedical applications, e.g., surgery probes, drug delivery, and photodynamic therapy.

Laser-Induced Fabrication of Micro-Optics on Bioresorbable Calcium Phosphate Glass for Implantable Devices.

In this study, a single-step nanosecond laser-induced generation of micro-optical features is demonstrated on an antibacterial bioresorbable Cu-doped calcium phosphate glass. The inverse Marangoni flow of the laser-generated melt is exploited for the fabrication of microlens arrays and diffraction gratings. The process is realized in a matter of few seconds and, by optimizing the laser parameters, micro-optical features with a smooth surface are obtained showing a good optical quality. The tunability of the microlens' dimensions is achieved by varying the laser power, allowing the obtaining of multi-focal microlenses that are of great interest for three-dimensional (3D) imaging. Furthermore, the microlens' shape can be tuned between hyperboloid and spherical. The fabricated microlenses exhibited good focusing and imaging performance and the variable focal lengths were measured experimentally, showing good agreement with the calculated values. The diffraction gratings obtained by this method showed the typical periodic pattern with a first-order efficiency of about 5.1%. Finally, the dissolution characteristics of the fabricated micropatterns were studied in a phosphate-buffered saline solution (PBS, pH = 7.4) demonstrating the bioresorbability of the micro-optical components. This study offers a new approach for the fabrication of micro-optics on bioresorbable glass, which could enable the manufacturing of new implantable optical sensing components for biomedical applications.

Volume nanogratings inscribed by ultrafast IR laser in alumino-borosilicate glasses.

Self-assembled nanogratings, inscribed by femtosecond laser writing in volume, are demonstrated in multicomponent alkali and alkaline earth containing alumino-borosilicate glasses. The laser beam pulse duration, pulse energy, and polarization, were varied to probe the nanogratings existence as a function of laser parameters. Moreover, laser-polarization dependent form birefringence, characteristic of nanogratings, was monitored through retardance measurements using polarized light microscopy. Glass composition was found to drastically impact the formation of nanogratings. For a sodium alumino-borosilicate glass, a maximum retardance of 168 nm (at 800 fs and 1000 nJ) could be measured. The effect of composition is discussed based on SiO2 content, B2O3/Al2O3 ratio, and the Type II processing window is found to decrease as both (Na2O + CaO)/Al2O3 and B2O3/Al2O3 ratios increase. Finally, an interpretation in the ability to form nanogratings from a glass viscosity viewpoint, and its dependency with respect to the temperature, is demonstrated. This work is brought into comparison with previously published data on commercial glasses, which further indicates the strong link between nanogratings formation, glass chemistry, and viscosity.

Regularization techniques for 3D surface reconstruction from four quadrant backscattered electron detector images.

In scanning electron microscopy (SEM), a four quadrants backscattered electron detector (FQBSD) provides signals that can be combined to obtain a tridimensional reconstruction of the surface. The main challenge of the reconstruction operation consists of integrating the gradient field obtained as the normalized signal difference from each pair of opposite quadrants. Owing to the presence of electronic noise that eventually turns into image noise, a least square integration approach has been widely adopted for surface reconstruction. In the present work, we demonstrate the possibility of adopting regularization techniques (Tichonov's and Dirichlet's) to the surface reconstruction from FQBSD images to reduce the distortions due to sensitivity variations amongst the detector quadrants or an imprecise alignment of the FQBSD with the gun axis. This allows for a substantial improvement in the 3D surface reconstruction quality in terms of resolution and reduction of artifacts. These procedures have been experimentally validated on AISI 316L stainless steel polished surfaces with hardness indentation and on laser-patterned aluminum and silicon samples showing promising results.

Fiber Optic Sensors for Harsh and High Radiation Environments in Aerospace Applications.

In the upcoming space revolutions aiming at the implementation of automated, smart, and self-aware crewless vehicles and reusable spacecraft, sensors play a significant role in the control systems. In particular, fiber optic sensors, with their small footprint and electromagnetic immunity, represent a great opportunity in aerospace. The radiation environment and the harsh conditions in which these sensors will operate represent a challenge for the potential user in the aerospace vehicle design and the fiber optic sensor specialist. We present a review that aims to be a primer in the field of fiber optic sensors in radiation environments for aerospace. We review the main aerospace requirements and their relationship with fiber optics. We also present a brief overview of fiber optics and sensors based on them. Finally, we present different examples of applications in radiation environments for aerospace applications.

Automated method for routine microplastic detection and quantification.

Microplastics (MPs) are a heterogeneous group of solid polymers with dimensions <5 mm, which are a widespread contaminant of the environment. Their ubiquitous presence grabbed researchers' attention in the last decade, and the problem of MPs detection and quantification is currently a topic of utmost importance. Most identification and quantification protocols are still based on the visual count, which is an extremely time-consuming and error-prone task due to operator subjectivity. To address such an issue, different software analysis procedures are available, but they mainly rely either on the use of optical microscopy, covering a minimal area for each sample (mm2 size), or they allow only the identification of the largest particles (>1 mm). Here, a semi-automatic innovative image processing method for quantifying and measuring microplastics on filter membrane substrates is presented and validated, comparing results with data obtained using visual counting performed by an experienced operator. The algorithm was tested with artificially generated microplastic images and samples taken from natural environments. Samples of Borgio Verezzi show cave sediment and Po River water were filtered on a glass filter membrane, and photographs were taken under 365 nm illumination, both without and with Nile Red staining. The proposed image analysis method, implemented in an easy-to-use Python script, was quite accurate and fast (about 10 s/image average processing time), showing an average deviation below 10 %, which is further reduced to about 8 % if the samples are stained with Nile Red.

On the Formation of Nanogratings in Commercial Oxide Glasses by Femtosecond Laser Direct Writing.

Nanogratings (NGs) are self-assembled subwavelength and birefringent nanostructures created by femtosecond laser direct writing (FLDW) in glass, which are of high interest for photonics, sensing, five-dimensional (5D) optical data storage, or microfluidics applications. In this work, NG formation windows were investigated in nine commercial glasses and as a function of glass viscosity and chemical composition. The NG windows were studied in an energy-frequency laser parameter landscape and characterized by polarizing optical microscopy and scanning electron microscopy (SEM). Pure silica glass (Suprasil) exhibits the largest NG window, whereas alkali borosilicate glasses (7059 and BK7) present the smallest one. Moreover, the NG formation windows progressively reduced in the following order: ULE, GeO2, B33, AF32, and Eagle XG. The NG formation window in glasses was found to decrease with the increase of alkali and alkaline earth content and was correlated to the temperature dependence of the viscosity in these glasses. This work provides guidelines to the formation of NGs in commercial oxide glasses by FLDW.

Ion-exchanged glass microrods as hybrid SERS/fluorescence substrates for molecular beacon-based DNA detection.

Ion-exchange in molten nitrate salts containing metal ions (i.e. silver, copper, etc.) represents a well-established technique able to modify the chemical-physical properties of glass materials. It is widely used not only in the field of integrated optics (IO) but also, more recently, in plasmonics due to the possibility to induce the formation of metal nanoparticles in the glass matrix by an ad hoc thermal post-process. In this work, the application of this technology for the realisation of low-cost and stable surface-enhanced Raman scattering (SERS) active substrates, based on soda-lime glass microrods, is reported. The microrods, with a radius of a few tens of microns, were obtained by cutting the end of an ion-exchanged soda-lime fibre for a length less than 1 cm. As ion source, silver nitrate was selected due to the outstanding SERS properties of silver. The ion-exchange and thermal annealing post-process parameters were tuned to expose the embedded silver nanoparticles on the surface of the glass microrods, avoiding the use of any further chemical etching step. In order to test the combined SERS/fluorescence response of these substrates, labelled molecular beacons (MBs) were immobilised on their surface for deoxyribonucleic acid (DNA) detection. Our experiments confirm that target DNA is attached on the silver nanoparticles and its presence is revealed by both SERS and fluorescence measurements. These results pave the way towards the development of low-cost and stable hybrid fibres, in which SERS and fluorescence interrogation techniques are combined in the same optical device.

Optimizing Gold Nanoparticle Size and Shape for the Fabrication of SERS Substrates by Means of the Langmuir-Blodgett Technique.

The Langmuir-Blodgett technique, in which a layer of nanoparticles is spread at the water/air interface and further transferred onto a solid support, is a versatile approach for the preparation of SERS substrates with a controllable arrangement of hotspots. In a previous work, we demonstrated that fine-tuning the lateral packing and subsequent seed growth of 10 nm gold nanoparticles led to a quasi-resonant enhanced in the SERS signal of a test analyte. Here, we explore further enhancements by modifying the size and shape of the spread gold nanoparticles in order to take advantage of the inherent interparticle repulsion mechanisms present at the interface. We show that the size of the used nanoparticles is also a determinant factor, which cannot be compensated by the subsequent electroless growth. We also show that, although the seeded growth leads to rough hotspots, the sensitivity can be optimized by self-assembling urchin-shaped nanoparticles, with a roughness that is fine-tuned a priori. Our results suggest an intriguing correlation between surface homogeneity and SERS signal enhancement, indicating that regular substrates will have the optimal performance.

Collagen Hybrid Formulations for the 3D Printing of Nanostructured Bone Scaffolds: An Optimized Genipin-Crosslinking Strategy.

Bone-tissue regeneration induced by biomimetic bioactive materials is the most promising approach alternative to the clinical ones used to treat bone loss caused by trauma or diseases such as osteoporosis. The goal is to design nanostructured bioactive constructs able to reproduce the physiological environment: By mimicking the natural features of bone tissue, the cell behavior during the regeneration process may be addressed. At present, 3D-printing technologies are the only techniques able to design complex structures avoiding constraints of final shape and porosity. However, this type of biofabrication requires complex optimization of biomaterial formulations in terms of specific rheological and mechanical properties while preserving high biocompatibility. In this work, we combined nano-sized mesoporous bioactive glasses enriched with strontium ions with type I collagen, to formulate a bioactive ink for 3D-printing technologies. Moreover, to avoid the premature release of strontium ions within the crosslinking medium and to significantly increase the material mechanical and thermal stability, we applied an optimized chemical treatment using ethanol-dissolved genipin solutions. The high biocompatibility of the hybrid system was confirmed by using MG-63 and Saos-2 osteoblast-like cell lines, further highlighting the great potential of the innovative nanocomposite for the design of bone-like scaffolds.

Characterization of sub-nanosecond pulsed laser amplification with Er:Yb co-doped phosphate glass fibers.

We present an experimental characterization of the amplification of sub-nanosecond duration laser pulses at a wavelength of 1538 nm in short custom-made Er:Yb phosphate glass fibers with different core diameters. The fibers vary in their diameter from 100 µm (highly multi-mode) down to 12 µm (single-mode). The peak power, energy per pulse, and spectral shape of the amplified signal are presented. With our input pulses, the measurements show that the large core diameter fibers do not increase the amplification of the 1538 nm signal. We believe this is due to the high re-absorption of the Er3+ ions in the phosphate fiber. The optimal fiber geometry was found to have a core diameter of 20 µm with a length of 14 cm. The maximum peak power is 8.25 kW, corresponding to a net gain of 10.9 dB, with a pulse duration of 0.7 ns and a repetition rate of 40 kHz.

In vivo testing of a bioresorbable phosphate-based optical fiber.

Optical fibers have recently attracted a noticeable interest for biomedical applications because they provide a minimally invasive method for in vivo sensing, imaging techniques, deep-tissue photodynamic therapy or optogenetics. The silica optical fibers are the most commonly used because they offer excellent optical properties, and they are readily available at a reasonable price. The fused silica is a biocompatible material, but it is not bioresorbable so it does not decompose in the body and the fibers must be ex-planted after in vivo use and their fragments can present a considerable risk to the patient when the fiber breaks. In contrast, optical fibers made of phosphate glasses can bring many benefits because such glasses exhibit good transparency in ultraviolet-visible and near-infrared regions, and their solubility in water can be tailored by changing the chemical composition. The bioresorbability and toxicity of phosphate glass-based optical fibers were tested in vivo on male laboratory rats for the first time. The fiber was spliced together with a standard graded-index multi-mode fiber pigtail and an optical probe for in vitro pH measurement was prepared by the immobilization of a fluorescent dye on the fiber tip by a sol-gel method to demonstrate applicability and compatibility of the fiber with common fiber optics.

Design, Synthesis, and Structure-Property Relationships of Er3+-Doped TiO2 Luminescent Particles Synthesized by Sol-Gel.

Titania particles doped with various concentrations of Erbium were synthesized by the sol-gel method followed by different heat treatments. The shape and the grain growth of the particles were noticeably affected by the concentration of Erbium and the heat treatment conditions. An infrared emission at 1530 nm, as well as green and red up-conversion emissions at 550 and 670 nm, were observed under excitation at 976 nm from all of the synthesized particles. The emission spectra and lifetime values appeared to be strongly influenced by the presence of the different crystalline phases. This work presents important guidelines for the synthesis of functional Er3+-doped titania particles with controlled and tailored spectroscopic properties for photonic applications.

Towards the use of bioresorbable fibers in time-domain diffuse optics.

In the last years bioresorbable materials are gaining increasing interest for building implantable optical components for medical devices. In this work we show the fabrication of bioresorbable optical fibers designed for diffuse optics applications, featuring large core diameter (up to 200 µm) and numerical aperture (0.17) to maximize the collection efficiency of diffused light. We demonstrate the suitability of bioresorbable fibers for time-domain diffuse optical spectroscopy firstly checking the intrinsic performances of the setup by acquiring the instrument response function. We then validate on phantoms the use of bioresorbable fibers by applying the MEDPHOT protocol to assess the performance of the system in measuring optical properties (namely, absorption and scattering coefficients) of homogeneous media. Further, we show an ex-vivo validation on a chicken breast by measuring the absorption and scattering spectra in the 500-1100 nm range using interstitially inserted bioresorbable fibers. This work represents a step toward a new way to look inside the body using optical fibers that can be implanted in patients. These fibers could be useful either for diagnostic (e. g. for monitoring the evolution after surgical interventions) or treatment (e. g. photodynamic therapy) purposes. Picture: Microscopy image of the 100 µm core bioresorbable fiber.

Effect of Partial Crystallization on the Structural and Luminescence Properties of Er3+-Doped Phosphate Glasses.

Er-doped phosphate glass ceramics were fabricated by melt-quenching technique followed by a heat treatment. The effect of the crystallization on the structural and luminescence properties of phosphate glasses containing Al2O3, TiO2, and ZnO was investigated. The morphological and structural properties of the glass ceramics were characterized by Field Emission-Scanning Electron Microscopy (FE-SEM), X-ray Diffraction (XRD), and micro-Raman spectroscopy. Additionally, the luminescence spectra and the lifetime values were measured in order to study the influence of the crystallization on the spectroscopic properties of the glasses. The volume ratio between the crystal and the glassy phases increased along with the duration of the heat treatment. The crystallization of the glass ceramics was confirmed by the presence of sharp peaks in the XRD patterns and different crystal phases were identified depending on the glass composition. Sr(PO3)2 crystals were found to precipitate in all the investigated glasses. As evidenced by the spectroscopic properties, the site of the Er3+ ions was not strongly affected by the heat treatment except for the fully crystallized glass ceramic which does not contain Al2O3, TiO2, and ZnO. An increase of the lifetime was also observed after the heat treatment of this glass. Therefore, we suspect that the Er3+ ions are incorporated in the precipitated crystals only in this glass ceramic.

Functionalized Surfaces with Tailored Wettability Determine Influenza A Infectivity.

Surfaces contaminated with pathogenic microorganisms contribute to their transmission and spreading. The development of "active surfaces" that can reduce or eliminate this contamination necessitates a detailed understanding of the molecular mechanisms of interactions between the surfaces and the microorganisms. Few studies have shown that, among the different surface characteristics, the wetting properties play an important role in reducing virus infectivity. Here, we systematically tailored the wetting characteristics of flat and nanostructured glass surfaces by functionalizing them with alkyl- and fluoro-silanes. We studied the effects of these functionalized surfaces on the infectivity of Influenza A viruses using a number of experimental and computational methods including real-time fluorescence microscopy and molecular dynamics simulations. Overall, we show that surfaces that are simultaneously hydrophobic and oleophilic are more efficient in deactivating enveloped viruses. Our results suggest that the deactivation mechanism likely involves disruption of the viral membrane upon its contact with the alkyl chains. Moreover, enhancing these specific wetting characteristics by surface nanostructuring led to an increased deactivation of viruses. These combined features make these substrates highly promising for applications in hospitals and similar infrastructures where antiviral surfaces can be crucial.

Near-field photocurrent nanoscopy on bare and encapsulated graphene.

Optoelectronic devices utilizing graphene have demonstrated unique capabilities and performances beyond state-of-the-art technologies. However, requirements in terms of device quality and uniformity are demanding. A major roadblock towards high-performance devices are nanoscale variations of the graphene device properties, impacting their macroscopic behaviour. Here we present and apply non-invasive optoelectronic nanoscopy to measure the optical and electronic properties of graphene devices locally. This is achieved by combining scanning near-field infrared nanoscopy with electrical read-out, allowing infrared photocurrent mapping at length scales of tens of nanometres. Using this technique, we study the impact of edges and grain boundaries on the spatial carrier density profiles and local thermoelectric properties. Moreover, we show that the technique can readily be applied to encapsulated graphene devices. We observe charge build-up near the edges and demonstrate a solution to this issue.

APPLIED PHYSICS. Mid-infrared plasmonic biosensing with graphene.

Infrared spectroscopy is the technique of choice for chemical identification of biomolecules through their vibrational fingerprints. However, infrared light interacts poorly with nanometric-size molecules. We exploit the unique electro-optical properties of graphene to demonstrate a high-sensitivity tunable plasmonic biosensor for chemically specific label-free detection of protein monolayers. The plasmon resonance of nanostructured graphene is dynamically tuned to selectively probe the protein at different frequencies and extract its complex refractive index. Additionally, the extreme spatial light confinement in graphene­up to two orders of magnitude higher than in metals­produces an unprecedentedly high overlap with nanometric biomolecules, enabling superior sensitivity in the detection of their refractive index and vibrational fingerprints. The combination of tunable spectral selectivity and enhanced sensitivity of graphene opens exciting prospects for biosensing.

An indium tin oxide-free polymer solar cell on flexible glass.

Future optoelectronic devices and their low-cost roll-to-roll production require mechanically flexible transparent electrodes (TEs) and substrate materials. Indium tin oxide (ITO) is the most widely used TE because of its high optical transmission and low electrical sheet resistance. However, ITO, besides being expensive, has very poor performance under mechanical stress because of its fragile oxide nature. Alternative TE materials have thus been sought. Here we report the development of a multilayer TiO2/Ag/Al-doped ZnO TE structure and an ITO-free polymer solar cell (PSC) incorporating it. Electro-optical performances close to those of ITO can be achieved for the proposed TE and corresponding PSC with an additional advantage in their mechanical flexibility, as demonstrated by the fact that the cell efficiency maintains 94% of its initial value (6.6%) after 400 cycles of bending, with 6 and 3 cm maximum and minimum radii, respectively. Instead of common plastic materials, our work uses a very thin (0.14 mm) flexible glass substrate with several benefits, such as the possibility of high-temperature processes, superior antipermeation properties against oxygen and moisture, and improved film adhesion.