A Non-Isothermal Pore Network Model of Primary Freeze Drying.

In this work, a non-isothermal pore network (PN) model with quasi-steady vapor transport and transient heat transfer is presented for the first time for the application of primary freeze drying. The pore-scale resolved model is physically based and allows for the investigation of correlations between spatially distributed structure and transport conditions. The studied examples were regular PN lattices with a significantly different structure, namely a spatially homogeneous PN, also denoted as monomodal PN, and a PN with significant structure variation, referred to as bimodal PN because of its bimodal pore size distribution. The material properties selected for the solid skeleton in this study are equivalent to those of maltodextrin. The temperature ranges applied here were -28 °C to -18 °C in the PN and -42 °C in the surrounding environment. The environmental vapor pressure was 10 Pa. The PNs were dried with constant temperature boundary conditions, and heat was transferred at the top side by the vapor leaving the PN. It is shown how the structural peculiarities affect the local heat and mass transfer conditions and result in a significant widening of the sublimation front in the case of the bimodal PN. The possibility of spatially and temporally resolved front structures is a unique feature of the PN model and allows the study of situations that are not yet described by classical continuum approaches, namely heterogeneous frozen porous materials. As demonstrated by the thin layers studied here, the pore-scale simulations are of particular interest for such situations, such as in lyomicroscopes or collagen scaffolds, where a length-scale separation between dry and ice-saturated regions is not possible.

Usability Testing of a Multi-Level Modeling Framework for Just-in-Time Adaptive Interventions (JITAIs) in Mobile Health.

The JITAI is an intervention design to support health behavior change. We designed a multi-level modeling framework for JITAIs and developed a proof-of-concept prototype (POC). This study aimed at investigating the usability of the POC by conducting two usability tests with students. We assessed the usability and the students' workload and success in completing tasks. In the second usability test, however, they faced difficulties in completing the tasks. We will work on hiding the complexity of the framework as well as improving the frontend and the instructions.

The Influence of Local Microstructure Inhomogeneities on Local Drying Kinetics during Freeze-Drying.

Freeze-drying is a gentle drying technique to dry high value products, such as pharmaceuticals, without impacting the quality of the product. However, this method is very time and cost intensive. It is known that larger pores reduce the duration of primary drying due to facilitated mass transport. However, next to the pore size, other structural parameters exist whose influence on drying kinetics is still unknown. Therefore, the aim of this article is to investigate the influence of the microstructure (pore size, shape and orientation) on local primary drying kinetics. In the study, freeze-drying experiments on maltodextrin and sucrose solutions (c1 = 0.05 and c2 = 0.15 w/w) were carried out in a lyomicroscope. Two-dimensional images were recorded during the whole drying process and in the dry state and analyzed on the movement of the sublimation front, pore size, orientation and shape. Different microstructures were created by using different freezing parameters, namely two different cooling rates and solid concentrations. It could be shown that for pores with a high aspect ratio, the pore orientation was more important for the drying kinetics than the pore size, while for pores with a lower aspect ratio the pore size was the decisive parameter.

Experimental Study of the Impact of Pore Structure on Drying Kinetics and Sublimation Front Patterns.

Freeze-drying frozen maltodextrin solutions with solid contents of 5% and 30% (w/w) was experimentally investigated using neutron imaging at PSI Villigen/Switzerland. Different solid contents, as well as annealing at -5 °C for 11 h, were used to modify the porous structure of the samples, which was quantified using X-ray computed tomography. Annealing of the 5% (w/w) sample, with a pore size distribution (PSD) of 23.7 ± 11.1 µm, yielded a very open pore space with high porosity (ε = 0.96) and a PSD of 33.0 ± 27.0 µm. In contrast, the higher solid content resulted in small, lamellar, narrow pores with high anisotropy and a porosity of ε = 0.65, as well as a PSD of 13.5 ± 4 µm. In operando neutron imaging was used to show the impact of the structure of frozen maltodextrin on the overall drying kinetics and shape of the sublimation front during freeze-drying. For this purpose, a freeze-drying stage was employed, which allowed a novel approach to time- and space-resolved monitoring of the ice phase. The sublimation front propagation was quantitatively analyzed based on ice saturation profiles and sublimation rates. The dependence of drying velocity on structure is nicely demonstrated by the data. In addition, it is shown that the sublimation front widened during freeze-drying, resulting in either rather concave or convex shape depending on morphological parameters.

Towards Adaptability of Just-in-Time Adaptive Interventions.

Just-in-time adaptive interventions (JITAIs) can promote behavior change in patients. It was the aim of our study to make JITAIs adaptable, i.e., to configure JITAIs for different purposes and to personalize them for different participants, whilst enabling central maintenance and integrated data analysis across deployments and individuals. We present a concept for adaptable JITAIs that was created following a design science approach. It builds on multi-level conceptual modeling and knowledge graphs and will be evaluated in user studies.

Development of an experimental setup for in situ visualization of lyophilization using neutron radiography and computed tomography.

This article shows a new conceptional design of an experimental setup for in situ visualization of the lyophilization process using neutron radiography and computed tomography and its validation. The setup is designed for the neutron imaging beam line ANTARES at FRM II, considering all the requirements for this method. Neutrons are ideally suited to detect water in a sample because of the high neutron attenuation of hydrogen, whereas other materials like aluminum have a low absorption of neutrons resulting in an image where the drying fronts in bulk materials are observable. Consisting of a freeze-drying cell and a sample-stick, the setup is basically inspired by a common freeze-drying unit. The cell is axial symmetrical to allow computed tomography measurements. The developed sample stick connects the vacuum cell with the measurement devices and the vacuum pump. Experiments were performed at FRM II, showing that the setup is functional. In addition, the experiments discovered some possibilities for improvements, which can be used in further measurements.