( 2019 2018 2017)
Aerosol deposition in human lungs – The new coronavirus disease is thought to spread mainly by droplet infection when an infected person coughs, sneezes, or talks and a bystander person inhale the droplets containing the pathogen of COVID-19. We applied the Stochastic Lung Deposition Model to quantify the deposition distribution of the droplets and aerosol particles containing SARS-CoV-2 (Centre for Energy Research). It was found that the probability of direct infection of the acinar airways due to inhalation of particles emitted by a bystander person is low. As the majority of the viruses deposited in the extrathoracic airways, we concluded that pneumonia must be preceded by infection of the upper airways in most cases.
Estimations for the particle size distribution, breathing parameters, and viral loads were taken from the literature. We assumed that the virus distribution is homogenous in the throat swab sample and that the amount of viruses in a particle is proportional to its volume. Hence, the virus content of the particles can be modeled with the Poisson distribution. Figure 1 shows the average number of viruses per particle and the probability that a particle contains virus as the function of particle size.
Figure 1. The average number of viruses in one particle (left axis and red lines) and the probability that a particle contains virus (right axis and blue lines) versus particle size for different viral loads in the throat.
Nanoparticle formation and emission during intense laser-matter interactions – We have characterized the emitted aerosol particles in the case of a laser-based additive manufacturing machine. Morphology, elemental composition, and oxidation state of selected metals (Cr, Mn, Fe, and Ni) were determined to describe their enrichment/depletion and oxidation compared to the original feedstock powder. Besides the SMPS measurements, aerosol samples were collected on PTFE filters, and size-fractionated samples on silicon wafers and adhesive carbon substrates by a cascade impactor. Scanning electron microscopy and energy dispersive spectroscopy were utilized to retrieve the morphology, and elemental composition, total-reflection, and microscopic X-ray fluorescence methods were used to determine the elemental composition, and the X-ray absorption near-edge structure method was used to study the oxidation state of selected metals in the aerosol particles. The results are summarized in . The fine and ultrafine particles released by AM machines (see figure 2) are potentially hazardous to the operators of the machines. Furthermore, the metallic nanoparticles can reduce the beam quality and the intensity of the laser during operation. We studied the effects of the different parameters on the properties of the created objects. The studied parameters were laser power, beam shape, quality, focusing, moving parameters, building strategies, parameters of the hatching and the perimeter, composition of the used powder, finishing strategies, shield gas flowrate, etc.
Figure 2. New particles formed during an AM process. Individual particles, smaller and larger aggregates are shown.
Measured size distributions and aerosol properties are in line with available literature data. Particle formation starts from below 10 nanometres, and the average particle size was between 50 and 60 nm during the process. When the cladding process was finished, the average size increased to around 100 nm within 30 minutes.
The analysis of the chemical composition of the released fine and ultrafine particles shows significant amounts of Fe, Cr, Mn, and Ni, where Ni, Cr, and Mn are toxic metals. The Mn enrichment in the ultrafine metal oxide particles, together with their large amount, increase their toxic potential with decreasing particle size .
Development of new know-how to produce special laser optical elements – I. Zero dispersion, minimal absorption damping filters (O.D. = 0.5, 1 or 2) in the wavelength range 500-1100 nm; II. Coatings for low transmission loss windows and focusing lenses for 1030 nm femtosecond lasers; III. Laser mirrors with R> 99.95% reflectance for 3350 nm laser wavelength; IV. Zero dispersion metal-dielectric laser mirrors with R> 99% reflectance for different spectral ranges.
Aerosol drug delivery/deposition in human lungs. – Experimental and numerical simulation methods were used to determine the efficiency of aerosol drugs, and a new method were proposed to enhance the efficiency of personalized therapies and reduce side effects. We studied the effects of the turbulences generated by the inhalation devices on the measured breathing parameters during standard spirometry. The observed turbulences may lead to false results during the measurement of the peak inhalation flow rate which may cause problems in the selection of the proper inhalation device used for the treatment of pulmonary diseases.
Development of the technology based on 3D metal printing. – Laser cladding by powder injection is a widely used technique in industrial applications such as additive manufacturing, parts repair, surface coating, etc. The powder used in laser cladding is normally a metallic alloy, and is injected into the system by coaxial or lateral nozzles. While the focused intense laser beam creates a melt pool on the surface of a substrate, the metallic powder stream also interacts with the laser and the particles deposit into the melt pool. Moving the substrate allows the melt pool to solidify and thus produces a track of solid metal which form a 3D object at the end (Fig.1.).
Figure 1. 3D printed object (during the printing process) with a laser-welding machine utilizing the direct energy deposition method.
Demo cubes were built from Ni-based metallic powder by a laser-welding machine utilizing the direct energy deposition method onto a stainless steel substrate. We studied the effects of the different parameters on the properties the created objects (Fig.2.). The studied parameters were laser power, beam shape and quality, focusing, moving parameters, building strategies, parameters of the hatching and the perimeter, composition of the used powder, finishing strategies, shield gas flowrate, etc.
Figure 2. Building process of a demo cube by laser cladding with metallic powder (left), a typical demo cube which was built to study the effects of the building parameters (middle), and a reconstructed surface with the Zygo NewViewTM 7100 interferometric surface profiler (right).
Nanoparticle formation and emission during intense laser-matter interactions. – We have studied the properties of the generated ultrafine smoke during the laser-welding processes. Different instruments were utilized to retrieve the properties of the released aerosol particles.
Particle formation during the process starts from below 10 nm, and the average particle size was between 50 and 60 nm. When the cladding process was finished, the average size increased to around 100 nm within 30 minutes period (Fig.3.). The generated smoke contains a considerable amount of ultrafine particles, where the filtration requires special techniques.
Figure 3. Temporal evolution of the measured size distribution of the particles emitted during a laser cladding process. The colour code represents number concentrations [1/cm3].
Health effects, occupational health – The health effects of the plume, which is released during 3D metal printing processes, were investigated by means of optical, electrostatic, inertial and spectroscopic techniques. While the typical size of metal powders, produced by inert gas atomization, span from 10 to 150 µm, it may contain alveolar as well as inhalable dust fractions and contain hazardous elements. We observed a considerable amount of newly formed aerosol particles in the plume with a size mainly below 1 µm. The fraction of the inhaled aerosol particles, which deposits in the lung, steeply increases with decreasing size in the ultrafine region, which may lead to occupational health problems.
Originally the 718G metal powder has a particle size range between 45 and 90 µm with mostly spherical shape. Fig. 4. shows the average elemental composition of the original powder. During the welding process the mass size distribution of the released particles shows a pronounced peak between 100 and 200 nm. The Ni-to-Cr ratio changed from approximately 2 (original metal powder) to around 0.67 (aerosol particles). Although Mn was not detected in the original powder, significant amount was released during laser welding. 95% of the Cr and 89% of the Ni was found in particles between 70 and 180 nm.
Figure 4. Elemental composition of the MetcoAdd 718G metallic powder detected with Energy Dispersive Spectroscopy.
Aerosol drug delivery/deposition in human lungs – In vitro experimental and in silico numerical simulation methods were used for the determination of the deposition distribution and deposition efficiency of aerosol drugs from pressurized metered dose inhalers and dry powder inhalers (widely utilized in the therapy of chronic pulmonary diseases) as a function of standard breathing parameters. The mass median aerodynamic diameter of the released particles was determined for different idealized inhalation waveforms, directly from the inhaler and after a realistic upper airway model. We found that the mass median aerodynamic diameter varies by a factor of 2 and decreases with increasing peak inspiratory flow and inhaled volume. It was measured to be approximately 10% lower after the upper airway. The stochastic lung deposition model was used to calculate the lung deposition of the medicament with each inhalation profile, taking into account the measured size distribution. We determined the minimum required inhalation flow for the examined dry powder inhalers for an acceptable level of lung deposition dose. Above 60 L/min peak inspiratory flow the lung deposition increases to above 50%, which may support a sufficient therapy. Our measurements showed that the length of the inhalation does not influence the lung deposition dose; peak inspiratory flow and inhaled volume are much more relevant factors. We presented a map of the deposition of the examined aerosol drug in the lung as a function of inhalation time and peak inspiratory flow (Fig.1.), which could be a useful tool for the doctors in the selection of the appropriate inhalation drug by knowing the correct inhalation parameters of the patient, these can help in the elaboration of personalized treatment.
Figure 1. The deposition efficiency map of a dry powder inhaler as a function of inhalation time (tin) and peak inspiratory flow (PIF).
Optical measurement techniques. — We have been involved in the development of prototype instruments for medical surgery applications based on short pulse and fibre lasers. The light scattering and absorption properties of model tissue materials were studied using different lasers and detection techniques, as well as the aerosol plume that is generated upon the interaction of intense laser light and model tissue materials. The spreading, concentration and optical properties of the smoke was studied using high-speed cameras and non-contact laser Doppler methods. We have been participating in the development of a new technology based on 3D metal printing with industrial partners.
Our previously developed optical method was utilized in a research project aimed at investigating the properties of absorbing aerosols (mineral dust - black carbon mixtures) in the Mediterranean region. The main aims of the project are to characterize the aging and mixing of light-absorbing aerosol layers, to assess the contribution of individual aerosol components to the radiative forcing of mixed absorbing aerosol layers, to implement complex particle morphologies in radiative forcing estimates, and to investigate potential links between the presence of absorbing particles, aerosol layer lifetime and removal. Our instrument was installed into a research aircraft monitoring the vertical and horizontal profile of aerosol contamination of the atmosphere in given trajectories.
The development of light sources of our patented expanded-beam imaging Spectro-ellipsometers are in progress in co-operation with the Institute for Technical Physics and Materials Science, Centre for Energy Research. Bio-photonic research was conducted to optimize the label-free, in-vivo fluorescence emission of different biological samples, according to their individual destruction thresholds in order to develop an optimal excitation laser source.
Aerosol drug delivery/deposition in human lungs. — The MMAD (mass median aerodynamic diameter) of the Symbicort® Turbuhaler dry powder inhaler (DPI) and the aerosol particle deposition in the upper airways was studied in case of different inhalation waveforms. For the detection of the aerosol size distribution, the Aerosol Particle Sizer (APS) Spectrometer was used. The effect of the breathing pattern on the MMAD was determined after the upper airways. With the help of the stochastic lung deposition model (SLDM), the amount of deposited particles in the lung was quantified. It was found that approximately 10% of the particles from the DPI deposit in the upper airways. The lung deposition of the drug from the DPI was calculated to be between 18 and 63% of the nominal dose, depending on the inhalation time and the peak inhalation flow.
Vibrational (Raman and infrared) spectroscopy based methods have been developed to determine the distribution of inhalation drugs (and other aerosols) in human airway replicas. The tested medication was introduced by metered dose inhaler into a realistic human lung tract prepared by 3D printing from computer tomographic data of human respiratory system. The deposited material was collected with silicon substrates attached to the hollow airway’s walls in different points. The analysis of the substrates was performed by Raman and infrared spectroscopic mapping of drug’s characteristic peak intensities over the surface. The method was verified by comparison with optical microscopic images recorded on the same surface area.
Study of optical properties of aerosols. — We have participated in the A-LIFE ERC project of the University of Vienna with PI Prof. Bernadett Weinzierl. The project is aimed at investigating the properties of absorbing aerosols (in particular mineral dust – black carbon (BC) mixtures) to characterize the aging and mixing of light-absorbing aerosol layers during their lifetime, to assess the contribution of individual aerosol components, in particular mineral dust and BC to the radiative forcing (RF) of mixed absorbing aerosol layers, to implement complex particle morphologies in RF estimates, and to investigate potential links between the presence of absorbing particles, aerosol layer lifetime and removal. We participated in the project by applying an optical method for the measurement of the optical and physical properties of ambient aerosols, which was developed by us in cooperation with the University of Vienna.
Optical thin film structures for advanced ultrafast applications. — We have continued our research concerning the development of optical thin film structures (high reflectors, output couplers, beam splitters, triple-band antireflective coatings etc.) for advanced femtosecond laser sources producing energetic light pulses in the near- and middle-infrared wavelength ranges. We have produced successfully sampling beam splitters on sapphire substrates for the French company Fastlite, working perfectly in their MIR laser system installed at ELI ALPS in Szeged already. We have developed new type of negative- or zero-dispersion multilayer mirror structures for our Japan partner also. The new laser mirror structures developed by us are very important in the development of new ultrafast high-power lasers which are able to shift the limits of the higher harmonic generation from the soft X-ray range to the hard X-ray range.
Optical measurement techniques serving the development of medical laser systems. — We have been involved in a project where the participants conduct research and development activities aiming at developing prototype instruments for medical surgery applications based on ultrashort pulse and fibre lasers. We have studied the light scattering and absorption properties of model tissue materials using different lasers and detection techniques. We have studied the surgical smoke that is generated upon the interaction of intense laser light and model tissue materials. In the frame of this study, we measured the size distribution of the surgical smoke with optical particle counter, aerodynamic particle counter and condensation particle counter, we measured the spread of the generated aerosols using laser Doppler anemometer, and collected samples with a cascade impactor for further analysis.