From Nanosystems to a Biosensing Prototype for an Efficient Diagnostic: A Special Issue in Honor of Professor Bansi D. Malhotra.

It has been proven that rapid bioinformatics analysis according to patient health profiles, in addition to biomarker detection at a low level, is emerging as essential to design an analytical diagnostics system to manage health intelligently in a personalized manner. Such objectives need an optimized combination of a nano-enabled sensing prototype, artificial intelligence (AI)-supported predictive analysis, and Internet of Medical Things (IoMT)-based bioinformatics analysis. Such a developed system began with a prototype demonstration of efficient diseases diagnostics performance is the future diseases management approach. To explore these aspects, the Special Issue planned for the nano-and micro-technology section of MDPI's Biosensors journal will honor and acknowledge the contributions of Prof. B.D. Malhotra, Ph.D., FNA, FNASc has made in the field of biosensors.

Emerging MXene-Polymer Hybrid Nanocomposites for High-Performance Ammonia Sensing and Monitoring.

Ammonia (NH3) is a vital compound in diversified fields, including agriculture, automotive, chemical, food processing, hydrogen production and storage, and biomedical applications. Its extensive industrial use and emission have emerged hazardous to the ecosystem and have raised global public health concerns for monitoring NH3 emissions and implementing proper safety strategies. These facts created emergent demand for translational and sustainable approaches to design efficient, affordable, and high-performance compact NH3 sensors. Commercially available NH3 sensors possess three major bottlenecks: poor selectivity, low concentration detection, and room-temperature operation. State-of-the-art NH3 sensors are scaling up using advanced nano-systems possessing rapid, selective, efficient, and enhanced detection to overcome these challenges. MXene-polymer nanocomposites (MXP-NCs) are emerging as advanced nanomaterials of choice for NH3 sensing owing to their affordability, excellent conductivity, mechanical flexibility, scalable production, rich surface functionalities, and tunable morphology. The MXP-NCs have demonstrated high performance to develop next-generation intelligent NH3 sensors in agricultural, industrial, and biomedical applications. However, their excellent NH3-sensing features are not articulated in the form of a review. This comprehensive review summarizes state-of-the-art MXP-NCs fabrication techniques, optimization of desired properties, enhanced sensing characteristics, and applications to detect airborne NH3. Furthermore, an overview of challenges, possible solutions, and prospects associated with MXP-NCs is discussed.

Autoimmunity roots of the thrombotic events after COVID-19 vaccination.

Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.

A unique view of SARS-CoV-2 through the lens of ORF8 protein.

Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host's interferon-mediated antiviral response. To understand the host's immune perspective in reference to the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.

Light-controlled growth factors release on tetrapodal ZnO-incorporated 3D-printed hydrogels for developing smart wound scaffold.

Advanced wound scaffolds that integrate active substances to treat chronic wounds have gained significant recent attention. While wound scaffolds and advanced functionalities have previously been incorporated into one medical device, the wirelessly triggered release of active substances has remained the focus of many research endeavors. To combine multiple functions including light-triggered activation, anti-septic, angiogenic, and moisturizing properties, we have developed a 3D printed hydrogel patch encapsulating vascular endothelial growth factor (VEGF) decorated with photoactive and antibacterial tetrapodal zinc oxide (t-ZnO) microparticles. To achieve the smart release of VEGF, t-ZnO was modified by chemical treatment and activated through UV/visible light exposure. This process would also make the surface rough and improve protein adhesion. The elastic modulus and degradation behavior of the composite hydrogels, which must match the wound healing process, were adjusted by changing t-ZnO concentrations. The t-ZnO-laden composite hydrogels can be printed with any desired micropattern to potentially create a modular elution of various growth factors. The VEGF decorated t-ZnO-laden hydrogel patches showed low cytotoxicity and improved angiogenic properties while maintaining antibacterial functions in vitro. In vivo tests showed promising results for the printed wound patches, with less immunogenicity and enhanced wound healing.

Glial cell responses on tetrapod-shaped graphene oxide and reduced graphene oxide 3D scaffolds in brain in vitro and ex vivo models of indirect contact.

Brain implants are promising instruments for a broad variety of nervous tissue diseases with a wide range of applications, e.g. for stimulation, signal recording or local drug delivery. Recently, graphene-based scaffold materials have emerged as attractive candidates as neural interfaces, 3D scaffolds, or drug delivery systems due to their excellent properties like flexibility, high surface area, conductivity, and lightweight. To date, however, there is a lack of appropriate studies of the foreign body response, especially by glial cells, towards graphene-based materials. In this work, we investigated the effects of macroscopic, highly porous (>99.9%) graphene oxide (GO) and reduced graphene oxide (rGO) (conductivity ∼1 S m-1) scaffolds with tailorable macro- and microstructure on human astrocyte and microglial cell viability and proliferation as well as expression of neuroinflammation and astrogliosis associated genes in an indirect contact approach. In this in vitro model, as well as ex vivo in organotypic murine brain slices, we could demonstrate that both GO and rGO based 3D scaffolds exert slight effects on the glial cell populations which are the key players of glial scar formation. These effects were in most cases completely abolished by curcumin, a known anti-inflammatory and anti-fibrotic drug that could in perspective be applied to brain implants as a protectant.

Macroscopic Silicone Microchannel Matrix for Tailored Drug Release and Localized Glioblastoma Therapy.

Localized therapy of the highly malignant brain tumor glioblastoma multiforme (GBM) could help to drastically improve the treatment efficiency and increase the patient's median survival. Here, a macroscopic PDMS matrix composed of interconnected microchannels for tailored drug release and localized GBM therapy is introduced. Based on a simple bottom-up fabrication method using a highly versatile sacrificial template, the presented strategy solves the scaling problem associated with the previously developed microchannel-based drug delivery systems, which were limited to two dimensions due to the commonly employed top-down microfabrication methods. Additionally, tailoring of the microchannel density, the fraction of drug-releasing microchannels and the macroscopic size of the drug delivery systems enabled precise adjustment of the drug release kinetics for more than 10 days. As demonstrated in a long-term GBM in vitro model, the release kinetics of the exemplarily chosen GBM drug AT101 could be tailored by variation of the microchannel density and the initial drug concentration, leading to diffusion-controlled AT101 release. Adapting a previously developed GBM treatment plan based on a sequential stimulation with AT101, measured anti-tumorigenic effects of free versus PDMS-released AT101 were comparable in human GBM cells and demonstrated efficient biological activity of PDMS-released AT101.

ZnAl2O4 decorated Al-doped ZnO tetrapodal 3D networks: microstructure, Raman and detailed temperature dependent photoluminescence analysis.

3D networks of Al-doped ZnO tetrapods decorated with ZnAl2O4 particles synthesised by the flame transport method were investigated in detail using optical techniques combined with morphological/structural characterisation. Low temperature photoluminescence (PL) measurements revealed spectra dominated by near band edge (NBE) recombination in the UV region, together with broad visible bands whose peak positions shift depending on the ZnO : Al mixing ratios. A close inspection of the NBE region evidences the effective doping of the ZnO structures with Al, as corroborated by the broadening and shift of its peak position towards the expected energy associated with the exciton bound to Al. Both temperature and excitation density-dependent PL results pointed to an overlap of multiple optical centres contributing to the broad visible band, with the peak position dependent on the Al content. While in the reference sample the wavelength of the green band remained unchanged with temperature, in the case of the composites, the deep level emission showed a blue shift with increasing temperature, likely due to distinct thermal quenching of the overlapping emitting centres. This assumption was further validated by the time-resolved PL data, which clearly exposed the presence of more than one optical centre in this spectral region. PL excitation analysis demonstrated that the luminescence features of the Al-doped ZnO/ZnAl2O4 composites revealed noticeable changes not only in deep level recombination, but also in the material's bandgap when compared with the ZnO reference sample. At room temperature, the ZnO reference sample exhibited free exciton resonance at ∼3.29 eV, whereas the peak position for the Al-doped ZnO/ZnAl2O4 samples occurred at ∼3.38 eV due to the Burstein-Moss shift, commonly observed in heavily doped semiconductors. Considering the energy shift observed and assuming a parabolic conduction band, a carrier concentration of ∼1.82 ×1019 cm-3 was estimated for the Al-doped ZnO/ZnAl2O4 samples.

Wet-Chemical Assembly of 2D Nanomaterials into Lightweight, Microtube-Shaped, and Macroscopic 3D Networks.

Despite tremendous efforts toward fabrication of three-dimensional macrostructures of two-dimensional (2D) materials, the existing approaches still lack sufficient control over microscopic (morphology, porosity, pore size) and macroscopic (shape, size) properties of the resulting structures. In this work, a facile fabrication method for the wet-chemical assembly of carbon 2D nanomaterials into macroscopic networks of interconnected, hollow microtubes is introduced. As demonstrated for electrochemically exfoliated graphene, graphene oxide, and reduced graphene oxide, the approach allows for the preparation of highly porous (> 99.9%) and lightweight (<2 mg cm-3) aeromaterials with tailored porosity and pore size as well as tailorable shape and size. The unique tubelike morphology with high aspect ratio enables ultralow-percolation-threshold graphene composites (0.03 S m-1, 0.05 vol%) which even outperform most of the carbon nanotube-based composites, as well as highly conductive aeronetworks (8 S m-1, 4 mg cm-3). On top of that, long-term compression cycling of the aeronetworks demonstrates remarkable mechanical stability over 10 000 cycles, even though no chemical cross-linking is employed. The developed strategy could pave the way for fabrication of various macrostructures of 2D nanomaterials with defined shape, size, as well as micro- and nanostructure, crucial for numerous applications such as batteries, supercapacitors, and filters.

Crystallography at the nanoscale: planar defects in ZnO nanospikes.

The examination of anisotropic nanostructures, such as wires, platelets or spikes, inside a transmission electron microscope is normally performed only in plan view. However, intrinsic defects such as growth twin interfaces could occasionally be concealed from direct observation for geometric reasons, leading to superposition. This article presents the shadow-focused ion-beam technique to prepare multiple electron-beam-transparent cross-section specimens of ZnO nanospikes, via a procedure which could be readily extended to other anisotropic structures. In contrast with plan-view data of the same nanospikes, here the viewing direction allows the examination of defects without superposition. By this method, the coexistence of two twin configurations inside the wurtzite-type structure is observed, namely and , which were not identified during the plan-view observations owing to superposition of the domains. The defect arrangement could be the result of coalescence twinning of crystalline nuclei formed on the partially molten Zn substrate during the flame-transport synthesis. Three-dimensional defect models of the twin interface structures have been derived and are correlated with the plan-view investigations by simulation.

Probing surface states in C60 decorated ZnO microwires: detailed photoluminescence and cathodoluminescence investigations.

ZnO microwires synthesised by the flame transport method and decorated with C60 clusters were studied in detail by photoluminescence (PL) and cathodoluminescence (CL) techniques. The optical investigations suggest that the enhanced near band edge recombination observed in the ZnO/C60 composites is attributed to the reduction of the ZnO band tail states in the presence of C60. Well-resolved free and bound excitons recombination, as well as 3.31 eV emission, are observed with increasing amount of C60 flooding when compared with the ZnO reference sample. Moreover, a shift of the broad visible emission to lower energies occurs with increasing C60 content. In fact, this band was found to be composed by two optical centres peaked in the green and orange/red spectral regions, presenting different lifetimes. The orange/red band exhibits faster lifetime decay, in addition to a more pronounced shift to lower energies, while the peak position of the green emission only shows a slight change. The overall redshift of the broad visible band is further enhanced by the change in the relative intensity of the mentioned optical centres, depending on the excitation intensity and on the C60 flooding. These results suggest the possibility of controlling/tuning the visible emission outcome by increasing the C60 amount on the ZnO surface due to the surface states present in the semiconductor. An adequate control of such phenomena may have quite beneficial implications when sensing applications are envisaged.

Complex shaped ZnO nano- and microstructure based polymer composites: mechanically stable and environmentally friendly coatings for potential antifouling applications.

Since the prohibition of tributyltin (TBT)-based antifouling paints in 2008, the development of environmentally compatible and commercially realizable alternatives is a crucial issue. Cost effective fabrication of antifouling paints with desired physical and biocompatible features is simultaneously required and recent developments in the direction of inorganic nanomaterials could play a major role. In the present work, a solvent free polymer/particle-composite coating based on two component polythiourethane (PTU) and tetrapodal shaped ZnO (t-ZnO) nano- and microstructures has been synthesized and studied with respect to mechanical, chemical and biocompatibility properties. Furthermore, antifouling tests have been carried out in artificial seawater tanks. Four different PTU/t-ZnO composites with various t-ZnO filling fractions (0 wt%, 1 wt%, 5 wt%, 10 wt%) were prepared and the corresponding tensile, hardness, and pull-off test results revealed that the composite filled with 5 wt% t-ZnO exhibits the strongest mechanical properties. Surface free energy (SFE) studies using contact angle measurements showed that the SFE value decreases with an increase in t-ZnO filler amounts. The influence of t-ZnO on the polymerization reaction was confirmed by Fourier transform infrared-spectroscopy measurements and thermogravimetric analysis. The immersion tests demonstrated that fouling behavior of the PTU/t-ZnO composite with a 1 wt% t-ZnO filler has been decreased in comparison to pure PTU. The composite with a 5 wt% t-ZnO filler showed almost no biofouling.

Three-dimensional Aerographite-GaN hybrid networks: single step fabrication of porous and mechanically flexible materials for multifunctional applications.

Three dimensional (3D) elastic hybrid networks built from interconnected nano- and microstructure building units, in the form of semiconducting-carbonaceous materials, are potential candidates for advanced technological applications. However, fabrication of these 3D hybrid networks by simple and versatile methods is a challenging task due to the involvement of complex and multiple synthesis processes. In this paper, we demonstrate the growth of Aerographite-GaN 3D hybrid networks using ultralight and extremely porous carbon based Aerographite material as templates by a single step hydride vapor phase epitaxy process. The GaN nano- and microstructures grow on the surface of Aerographite tubes and follow the network architecture of the Aerographite template without agglomeration. The synthesized 3D networks are integrated with the properties from both, i.e., nanoscale GaN structures and Aerographite in the form of flexible and semiconducting composites which could be exploited as next generation materials for electronic, photonic, and sensors applications.

Statistical analysis of gold nanoparticle-induced oxidative stress and apoptosis in myoblast (C2C12) cells.

Nanoscale gold particles (Au-NPs) with a diameter below 20nm are notably important candidates for various important applications because of their extraordinary quantum size effects. Their high surface area-to-volume ratio facilitates their very high reactivities; therefore, they can be utilised in different ways in biomedical applications. For example, these nanoparticles can penetrate into cells and bind with proteins or DNA and are therefore potential nanostructures employed for sensing and detecting various biological identities. In the present work, we synthesised Au-NPs via a colloidal process using chloroauric acid (HAuCl4·4H2O) and trisodium citrate dihydrate (N3C6H5O7) as a reducing agent. The shape evolution and the structural properties of these NPs were investigated in detail using TEM and high resolution HR-TEM investigations. Different doses of Au NPs have been applied to treat C2C12 myoblast cells in a 24-h incubation period, and a dose-dependent study has also been performed. The cells were cultivated in DMEM with FBS and antibiotics (strepto-penicillin) at 37°C in a 5% humidified environment of CO2 and 95% air. Cell viability analysis using MTT assays revealed that increased concentration of Au NPs (100-1000 ng/mL) resulted in a decreased density of cells. The amount of reactive oxygen species (ROS) in C2C12 cells analysed with Au-NPs (in a dose-dependent manner), and the RT-PCR data demonstrated the up-regulation of caspase-3 and caspase-7 genes in C2C12 cells after treatment with Au-NPs. These results have been confirmed by detailed confocal microscopy (CLSM) studies. In addition, the quantitative analysis of the Au-NPs was also confirmed by statistical analytical parameters, such as precision, accuracy, linearity, limits of detection (LOD) and limit of quantitation (LOQ), quantitative recoveries and relative standard deviation (RSD), and the analyses again exhibited a significant and large effect of Au NPs on C2C12 cells.

Reactive oxygen species mediated bacterial biofilm inhibition via zinc oxide nanoparticles and their statistical determination.

The formation of bacterial biofilm is a major challenge in clinical applications. The main aim of this study is to describe the synthesis, characterization and biocidal potential of zinc oxide nanoparticles (NPs) against bacterial strain Pseudomonas aeruginosa. These nanoparticles were synthesized via soft chemical solution process in a very short time and their structural properties have been investigated in detail by using X-ray diffraction and transmission electron microscopy measurements. In this work, the potential of synthesized ZnO-NPs (∼ 10-15 nm) has been assessed in-vitro inhibition of bacteria and the formation of their biofilms was observed using the tissue culture plate assays. The crystal violet staining on biofilm formation and its optical density revealed the effect on biofilm inhibition. The NPs at a concentration of 100 µg/mL significantly inhibited the growth of bacteria and biofilm formation. The biofilm inhibition by ZnO-NPs was also confirmed via bio-transmission electron microscopy (Bio-TEM). The Bio-TEM analysis of ZnO-NPs treated bacteria confirmed the deformation and damage of cells. The bacterial growth in presence of NPs concluded the bactericidal ability of NPs in a concentration dependent manner. It has been speculated that the antibacterial activity of NPs as a surface coating material, could be a feasible approach for controlling the pathogens. Additionally, the obtained bacterial solution data is also in agreement with the results from statistical analytical methods.

Single step integration of ZnO nano- and microneedles in Si trenches by novel flame transport approach: whispering gallery modes and photocatalytic properties.

Direct growth of quasi-one-dimensional nano- and microstructures in desired places of complex shaped substrates using simple growth methods is highly demanded aspect for various applications. In this work, we have demonstrated direct integration of ZnO nano- and microneedles into Si trenches by a novel flame transport synthesis approach in a single fabrication step. Growth of partially and fully covered or filled trenches in Si substrate with ZnO nano- and microneedles has been investigated and is discussed here. Detailed microstructural studies revealed the evolution of the ZnO nano- and microneedles as well as their firm adhesion to the wall in the Si trenches. Micro-photoluminescence measurements at different locations along the length of needles confirmed the good crystalline quality and also the presence of whispering gallery mode resonances on the top of needles due to their hexagonal shape. Faceted ZnO nano- and microstructures are also very important candidates with regard to photocatalytic activity. First, photocatalytic measurements from the grown ZnO nano- and microneedles have shown strong degradation of methylene blue, which demonstrate that these structures can be of significant interest for photocatalysis and self-cleaning chromatography columns.

Toxicity of functional nano-micro zinc oxide tetrapods: impact of cell culture conditions, cellular age and material properties.

With increasing production and applications of nanostructured zinc oxide, e.g., for biomedical and consumer products, the question of safety is getting more and more important. Different morphologies of zinc oxide structures have been synthesized and accordingly investigated. In this study, we have particularly focused on nano-micro ZnO tetrapods (ZnO-T), because their large scale fabrication has been made possible by a newly introduced flame transport synthesis approach which will probably lead to several new applications. Moreover, ZnO-T provide a completely different morphology then classical spherical ZnO nanoparticles. To get a better understanding of parameters that affect the interactions between ZnO-T and mammalian cells, and thus their biocompatibility, we have examined the impact of cell culture conditions as well as of material properties on cytotoxicity. Our results demonstrate that the cell density of fibroblasts in culture along with their age, i.e., the number of preceding cell divisions, strongly affect the cytotoxic potency of ZnO-T. Concerning the material properties, the toxic potency of ZnO-T is found to be significantly lower than that of spherical ZnO nanoparticles. Furthermore, the morphology of the ZnO-T influenced cellular toxicity in contrast to surface charges modified by UV illumination or O2 treatment and to the material age. Finally, we have observed that direct contact between tetrapods and cells increases their toxicity compared to transwell culture models which allow only an indirect effect via released zinc ions. The results reveal several parameters that can be of importance for the assessment of ZnO-T toxicity in cell cultures and for particle development.

Tin oxide nanowires suppress herpes simplex virus-1 entry and cell-to-cell membrane fusion.

The advent of nanotechnology has ushered in the use of modified nanoparticles as potential antiviral agents against diseases such as herpes simplex virus 1 and 2 (HSV-1) (HSV-2), human immunodeficiency virus (HIV), monkeypox virus, and hepatitis B virus. Here we describe the application of tin oxide (SnO(2)) nanowires as an effective treatment against HSV-1 infection. SnO(2) nanowires work as a carrier of negatively charged structures that compete with HSV-1 attachment to cell bound heparan sulfate (HS), therefore inhibiting entry and subsequent cell-to-cell spread. This promising new approach can be developed into a novel form of broad-spectrum antiviral therapy especially since HS has been shown to serve as a cellular co-receptor for a number of other viruses as well, including the respiratory syncytial virus, adeno-associated virus type 2, and human papilloma virus.

Prophylactic, therapeutic and neutralizing effects of zinc oxide tetrapod structures against herpes simplex virus type-2 infection.

The attachment of Herpes simplex virus type-2 (HSV-2) to a target cell requires ionic interactions between negatively charged cell surface co-receptor heparan sulfate (HS) and positively charged residues on viral envelop glycoproteins, gB and gC. Effective blocking of this first step of HSV-2 pathogenesis demonstrates significant prophylactic effects against the viral disease; any in vitro therapeutic effects of blocking this interaction, however, are not clear. Here, we provide new evidence that zinc oxide tetrapod micro-nanostructures synthesized by flame transport approach significantly block HSV-2 entry into target cells and, in addition, demonstrate the potential to stop the spread of the virus among already infected cells. The zinc oxide tetrapods (ZnOTs) also exhibit the ability to neutralize HSV-2 virions. Natural target cells such as human vaginal epithelial and HeLa cells showed highly reduced infectivity when infected with HSV-2 virions that were pre-incubated with the ZnOTs. The mechanism behind the ability of ZnOTs to prevent, neutralize or reduce HSV-2 infection relies on their ability to bind the HSV-2 virions. We used fluorescently labeled ZnOTs and GFP-expressing HSV-2 virions to demonstrate the binding of the ZnOTs with HSV-2. We also show that the binding and hence, the antiviral effects of ZnOTs can be enhanced by illuminating the ZnOTs with UV light. Our results provide new insights into the anti-HSV-2 effects of ZnOT and rationalize their development as a HSV-2 trapping agent for the prevention and/or treatment of infection. The observed results also demonstrate that blocking HSV-2 attachment can have prophylactic as well as therapeutic applications.

Solvent free fabrication of micro and nanostructured drug coatings by thermal evaporation for controlled release and increased effects.

Nanostructuring of drug delivery systems offers many promising applications like precise control of dissolution and release kinetics, enhanced activities, flexibility in terms of surface coatings, integration into implants, designing the appropriate scaffolds or even integrating into microelectronic chips etc. for different desired applications. In general such kind of structuring is difficult due to unintentional mixing of chemical solvents used during drug formulations. We demonstrate here the successful solvent-free fabrication of micro-nanostructured pharmaceutical molecules by simple thermal evaporation (TE). The evaporation of drug molecules and their emission to a specific surface under vacuum led to controlled assembling of the molecules from vapour phase to solid phase. The most important aspects of thermal evaporation technique are: solvent-free, precise control of size, possibility of fabricating multilayer/hybrid, and free choice of substrates. This could be shown for twenty eight pharmaceutical substances of different chemical structures which were evaporated on surfaces of titanium and glass discs. Structural investigations of different TE fabricated drugs were performed by atomic force microscopy, scanning electron microscopy and Raman spectroscopy which revealed that these drug substances preserve their structurality after evaporation. Titanium discs coated with antimicrobial substances by thermal evaporation were subjected to tests for antibacterial or antifungal activities, respectively. A significant increase in their antimicrobial activity was observed in zones of inhibition tests compared to controls of the diluted substances on the discs made of paper for filtration. With thermal evaporation, we have successfully synthesized solvent-free nanostructured drug delivery systems in form of multilayer structures and in hybrid drug complexes respectively. Analyses of these substances consolidated that thermal evaporation opens up the possibility to convert dissoluble drug substances into the active forms by their transfer onto a specific surface without the need of their prior dissolution.