Drug diffusivities in nanofibrillar cellulose hydrogel by combined time-resolved Raman and fluorescence spectroscopy

Hydrogels, natural and synthetic origin, are actively studied for their use for implants and payload carriers. These biomaterials for delivery systems have enormous potential in basic biomedical research, drug development, and long-term delivery of biologics. Nanofibrillated cellulose (NFC) hydrogels, both natural and anionic (ANFC) ones, allow drug loading for immediate and controlled release via the slow drug dissolution of solid drug crystals into hydrogel and its subsequent release. This property makes NFC originated hydrogels an interesting non-toxic and non-human origin material as drug reservoir for long-term controlled release formulation or implant for patient care. A compelling tool for studying NFC hydrogels is Raman spectroscopy, which enables to resolve the chemical structures of different molecules in a high-water content like hydrogels, since Raman spectroscopy is insensitive to water molecules. That offers real time investigation of label-free drugs and their release in high-water-content media. Despite the huge potential of Raman spectroscopy in bio-pharmaceutical applications, the strong fluorescence background of many drug samples masking the faint Raman signal has restricted the widespread use of it. In this study we used a Raman spectrometer capable of suppressing the unpleasant fluorescence background by combining a pulsed laser and time-resolved complementary metal-oxide-semiconductor (CMOS) singlephoton avalanche diode (SPAD) line sensor for the label-free investigation of Metronidazole and Vitamin C diffusivities in ANFC. The results show the possibility to modulate the ANFC-based implants and drug delivery systems, when the release rate needs to be set to a desired value. More importantly, the now developed label free real-time method is universal and can be adapted to any hydrogel/drug combination for producing reliable drug diffusion coefficient data in complex and heterogeneous systems, where traditional sampling-based methods are cumbersome to use. The wide temporal range of the time-resolved CMOS SPAD sensors makes it possible to capture also the fluorescence decay of samples, giving rise to a combined time-resolved Raman and fluorescence spectroscopy, which provides additional information on the chemical, functional and structural changes in samples.Peer reviewe

Position-sensitive devices and sensor systems for optical tracking and displacement sensing applications

Abstract This thesis describes position-sensitive devices (PSDs) and optical sensor systems suitable for industrial tracking and displacement sensing applications. The main application areas of the proposed sensors include automatic pointing of a rangefinder beam and measuring the lateral displacement of an object. A conventional tracking sensor is composed of a laser illuminator, a misfocused quadrant detector (QD) receiver and a corner cube retroreflector (CCR) attached to the target. The angular displacement of a target from the receiver optical axis is detected by illuminating the target and determining the direction of the reflection using the QD receiver. The main contribution of the thesis is related to the modifications proposed for this conventional construction in order to make its performance sufficient for industrial applications that require a few millimetre to submillimetre accuracy. The work includes sensor optical construction modifications and the designing of new types of PSDs. The conventional QD-based sensor, although electrically very sensitive, is not considered optimal for industrial applications since its precision is severely hampered by atmospheric turbulence due to the misfocusing needed for its operation. Replacing the CCR with a sheet reflector is found to improve the precision of the conventional sensor construction in outdoor beam pointing applications, and is estimated to allow subcentimetre precision over distances of up to 100 m under most operating conditions. Submillimetre accuracy is achievable in close-range beam pointing applications using a small piece of sheet reflector, coaxial illumination and a focused QD receiver. Polarisation filtering is found to be effective in eliminating the main error contributor in close-range applications, which is low reflector background contrast, especially in cases when a sheet reflector has a specularly reflecting background. The tracking sensor construction is also proposed for measuring the aiming trajectory of a firearm in an outdoor environment. This time an order of magnitude improvement in precision is achieved by replacing the QD with a focused lateral effect photodiode (LEP). Use of this construction in cases of intermediate atmospheric turbulence allows a precision better than 1 cm to be achieved up to a distance of 300 m. A method based on averaging the positions of multiple reflectors is also proposed in order to improve the precision in turbulence-limited cases. Finally, various types of custom-designed PSDs utilising a photodetector array structure are presented for long-range displacement sensing applications. The goal was to be able to replace the noisy LEP with a low-noise PSD without compromising the low turbulence sensitivity achievable with the LEP. An order of magnitude improvement in incremental sensitivity is achievable with the proposed array PSDs

Properties and suitability of liquid electrode plasma optical emission spectrometry (LEP-OES) for the determination of potassium, lithium, iron, and zinc in aqueous sample solutions

Abstract The effects of different parameters and the nitric acid concentration on the sensitivity and repeatability of elemental analysis were characterized for liquid electrode plasma optical emission spectrometry (LEP-OES). In addition, internal standardization for LEP-OES was investigated. The developed LEP-OES method was used for the determination of lithium, potassium, iron, and zinc in aqueous solutions and in samples with high acid concentrations after microwave-assisted digestion. The results were compared with those obtained by inductively coupled plasma — optical emission spectrometry. The sensitivity was improved when the plasma parameters were optimized. In addition, some improvement in the accuracy and reproducibility of the results was achieved when internal standardization by gold was employed. However, due to the strong matrix effects, the calibration standards should be made as similar as possible to the sample matrix

Instrument and method for measuring ice accretion in mixed-phase cloud conditions

Abstract The ICEMET-sensor is a novel cloud droplet and particle imaging instrument which measures icing conditions by determining the number and sizes of the supercooled droplets in a known air volume. The sensor captures digital holograms from 0.5 cm 3 sample volume with a maximum rate of 3.0 cm 3 /s. This lensless imaging instrument uses a computational imaging method to reconstruct the shadow images of the objects in the measurement volume. The size, position and shape descriptors of the individual particles and droplets are calculated and saved into a database. This data can be used to separate between cloud droplets and other particles. The calculated features are used to determine the two essential parameters needed for ice accretion modeling according to the ISO 12494 icing standard: liquid water content (LWC) of the air and median volume diameter (MVD) of the droplets. The basic working principle of the sensor and the image processing method are described. The performance of the sensor was tested in a wind tunnel under mixed-phase icing conditions. The measured LWC and MVD values were used to model ice accretion using the ISO 12494 icing standard for rotating cylinders. The modeled ice accretions were compared with weighed ice masses obtained from the wind tunnel with the same sized cylinder. The results show that accurate droplet size measurement and separation between droplets and ice crystals are essential for estimating the ice accretion rate properly. Without filtering out the ice crystals, the calculated accretion rates were overestimated by 65.6 % on average

Study of the aerodynamic sampling effects of a holographic cloud droplet instrument

Abstract Computational fluid dynamics and particle tracing simulations are presented for a cloud droplet sensor. Airspeeds and streamlines around the sensor are calculated at several wind speeds and their effect on the droplet sampling are examined. Particle tracing is used to study the effect of different wind speeds and droplet sizes on the sampling of the cloud droplets. Simulated droplet concentrations are confirmed by comparing them with measured wind tunnel data. Results demonstrate clear sampling effects that are functions of both wind speed and droplet size. Optimal compromise between maximal measurement volume and sampling effects is found and a simple approximation for sensor’s sampling bias is presented. The results show that CFD simulations can give valuable information about the sampling of droplets in an ideal environment with known droplet concentrations. Even in a wind tunnel, the true test conditions are often impossible to accurately determine. Thus by simulating the sampling effects in different conditions, the sensor can be calibrated for a wide range of naturally occurring cloud conditions

Measuring atmospheric icing rate in mixed-phase clouds using filtered particle data

Abstract In-cloud icing of objects is caused by supercooled microscopic water droplets carried by the wind. To estimate the icing rate of objects in such conditions, the liquid water content (LWC) of the icing cloud and the median volume diameter (MVD) of the droplets are measured. Mixed-phase clouds also contain ice crystals that must be ruled out in order to avoid the overestimation of the icing rate. Typically, cloud droplet instruments are not able to do this. A particle imaging instrument icing condition evaluation method (ICEMET) was used to observe in-cloud icing conditions. This lensless device uses a computational imaging method to reconstruct the shadow images of the microscopic objects. The size, position, and shape descriptors of each particle are measured. These data are then used to filter out the ice crystals. The droplet size distribution and the size of the measurement volume are used to determine the LWC and MVD. The performance of the instrument was tested under mixed-phase icing conditions in a wind tunnel and on a wind turbine. The measured LWC and MVD values were used to model the ice accretion on a cylinder-shaped object according to the ISO 12494:2017 icing standard. In the wind tunnel, the modeled ice mass was compared with the weighed ice mass collected by a cylinder. According to our results, ice accretion rates were overestimated by 65.6% on average without filtering out the ice crystals. Thus, the ability to distinguish between droplets and ice crystals is essential for estimating the icing rate properly

Predicting scattering properties of fiber suspensions using Mie theory and probabilistic cross-sectional diameter of fibers

Abstract Scattering of visible light by micrometer-scale natural wood fibers is usually treated by assuming fibers to be perfect long cylindrical scatterers. In industrial processes, however, fibers experience deformations and are far from ideal cylinders. Variation in fiber morphology affects their scattering properties and it poses a challenge for reliable process measurements. In this paper, we have studied experimentally scattering of both deformed natural and ideal artificial non-absorbing fibers in aqueous suspension and their response to mass concentration of fibers. Experimental results are compared with the predictions of the Mie theory which is combined with cross-sectional diameter probability distribution of fibers. It is shown that the diameter distribution of the fibers together with Mie theory provides results that agree with experiments in case of both natural and ideal fibers

Droplet size distribution and liquid water content monitoring in icing conditions with the ICEMET sensor

Abstract Field measurement results from a novel optical cloud droplet monitoring sensor designed for icing conditions monitoring are presented. The sensor has been demonstrated at two sites in northern Finland; first at Global Atmosphere Watch Station in Pallas together with a reference icing sensor and secondly mounted on a wind turbine nacelle in eastern Finland in 2017. Test runs in an icing wind tunnel have been made where more severe icing conditions were generated. The ICEMET sensor measurement principle is based on capturing the images of cloud droplets and ice particles. Droplet properties, such as droplet size distribution (DSD) and median volume diameter (MVD), are acquired by means of image analysis of the captured images. The images and the calculated features (size, location, shape descriptors) of all the found particles are saved in a database. A volume of 0.5 cm³ is imaged in a single frame. The liquid water content (LWC) is calculated based on this known sample volume in combination with the droplet data acquired from the image analysis of the found and filtered particles (droplets only). The sensor is typically freely rotating — it aligns itself against the wind by a wing on the backside. In the rotating configuration, the maximum sampling rate is 3 cm³/s. The movement of the particles inside sample volume is frozen in the images by a nanosecond scale light flash, making the sample volume independent of the wind speed. The maximum wind speed tested in a wind tunnel with the sensor is 40 m/s. The cloud droplet sizes from 5 to 200 microns are measured by the ICEMET sensor. In this paper LWC and MVD measurement results from the field tests and the wind tunnel tests with the sensor are presented and discussed. The webpages for the sensor can be found at https://www.oulu.fi/icemet

Weighing cylinder instrument with controlled de-icing for ice accretion measurements

Abstract Ice collecting cylinders are widely used in atmospheric icing measurements to predict the amount of ice collected by various structures in an icing environment. The mass of the accreted ice on the surface of cylinders and other object shapes can be modelled using ISO12494:2017 standard Atmospheric icing of structures which links atmospheric parameters and various object shapes. Reliable measurement of the icing conditions (icing rate) assumes an ideal cylinder-shaped surface with a fixed diameter meaning that the accreted ice layer during the measurement should be thin and free of inconsistency in ice accretion. Thus, any accreted ice should be removed before starting the measurement and the weighing sensor has to be sensitive enough to accurately measure ice loads of few tens of grams. A novel rotating cylinder based instrument, IceMan (Ice Manager), was constructed according to the guidelines of the icing standard. Unlike the other similar devices, it has ability to remove the accreted ice before each measurement and to measure ice masses from 0 to 260 g with a reasonable uncertainty of ±1.5 g making it potentially highly suitable for the assessment of icing conditions. Agreement between the ice accretion rate measured with the IceMan instrument and the icing rate calculated using the ISO 12494:2017 standard was confirmed with field measurements. The results show good agreement within the validity range of the icing model of the standard

A rotating holographic imager for stationary cloud droplet and ice crystal measurements

Abstract An optical cloud droplet and ice crystal measurement system ICEMET (icing condition evaluation method), designed for present icing condition monitoring in field conditions, is presented. The aim in this work has been to develop a simple but precise imaging technique to measure the two often missing parameters needed in icing rate calculations caused by icing clouds—the droplet size distribution (DSD) and the liquid water content (LWC) of the air. The measurement principle of the sensor is based on lens-less digital in-line holographic imaging. Cloud droplets and ice crystals are illuminated by a short laser light pulse and the resulting hologram is digitally sampled by a digital image sensor and the digital hologram is then numerically analyzed to calculate the present DSD and LWC values. The sensor has anti-icing heating power up to 500 W and it is freely rotating by the wind for an optimal sampling direction and aerodynamics. A volume of 0.5 cm³ is sampled in each hologram and the maximum sampling rate is 3 cm³/s. Laboratory tests and simulations were made to ensure the adequate operation of the measurement sensor. Computational flow dynamics simulations showed good agreement with droplet concentration distributions measured from an icing wind tunnel. The anti-icing heating of the sensor kept the sensor operational even in severe icing conditions; the most severe test conditions were the temperature − 15 °C, wind speed 20 m/s and the LWC 0.185 g/m³. The verification measurements made using NIST traceable monodisperse particle standard glass spheres showed that the ICEMET sensor measurement median diameter 25.54 µm matched well with 25.60 µm ± 0.70 µm diameter confidence level given by the manufacturer