Cell Cluster Sorting in Automated Differentiation of Patient-specific Induced Pluripotent Stem Cells Towards Blood Cells.

Induced pluripotent stem cells (iPS cells) represent a particularly versatile stem cell type for a large array of applications in biology and medicine. Taking full advantage of iPS cell technology requires high throughput and automated iPS cell culture and differentiation. We present an automated platform for efficient and robust iPS cell culture and differentiation into blood cells. We implemented cell cluster sorting for analysis and sorting of iPS cell clusters in order to establish clonal iPS cell lines with high reproducibility and efficacy. Patient-specific iPS cells were induced to differentiate towards hematopoietic cells via embryoid body (EB) formation. EB size impacts on iPS cell differentiation and we applied cell cluster sorting to obtain EB of defined size for efficient blood cell differentiation. In summary, implementing cell cluster sorting into the workflow of iPS cell cloning, growth and differentiation represent a valuable add-on for standard and automated iPS cell handling.

Design of an aircraft generator with radial force control.

With the increasing electrical energy demands in aviation propulsion systems, the increase in the onboard generators' power density is inevitable. During the flight, forces coming from the gearbox or gyroscopic forces generated by flight manoeuvres like take-off and landing can act on the generators' bearings, which can lead to wear and fatigue in the bearings. Utilizing the radial force control concept in the electrical machine can relieve loads from the bearings that not only minimize the bearing losses but also increase bearing life. The objective of the MAGLEV project (Measurement and Analysis of Generator bearing Loads and Efficiency with Validation) is to study, demonstrate, and test a new class of high-speed generators with radial force control. In this paper, design steps of this type of generator and its test rig are presented and the measurement methodology used for radial force control is explained. The concept is developed in an electrical machine and is validated on a test rig by measuring required parameters like shaft displacement, vibrations and bearing temperature. Additionally, the friction moment of each generator's bearings is measured and validated in a separate test rig under comparable conditions to the bearing loads in the generator. Therefore, a novel approach to determine precisely the bearing friction in a radial load unit, rotatably supported by an additional needle bearing is used, which shows a good agreement with the calculated friction. Furthermore, new calculation methods for the operating behavior of cylindrical roller bearings with clearance are presented, which are utilized in the generator test rig.

A Survey on AI-Driven Digital Twins in Industry 4.0: Smart Manufacturing and Advanced Robotics.

Digital twin (DT) and artificial intelligence (AI) technologies have grown rapidly in recent years and are considered by both academia and industry to be key enablers for Industry 4.0. As a digital replica of a physical entity, the basis of DT is the infrastructure and data, the core is the algorithm and model, and the application is the software and service. The grounding of DT and AI in industrial sectors is even more dependent on the systematic and in-depth integration of domain-specific expertise. This survey comprehensively reviews over 300 manuscripts on AI-driven DT technologies of Industry 4.0 used over the past five years and summarizes their general developments and the current state of AI-integration in the fields of smart manufacturing and advanced robotics. These cover conventional sophisticated metal machining and industrial automation as well as emerging techniques, such as 3D printing and human-robot interaction/cooperation. Furthermore, advantages of AI-driven DTs in the context of sustainable development are elaborated. Practical challenges and development prospects of AI-driven DTs are discussed with a respective focus on different levels. A route for AI-integration in multiscale/fidelity DTs with multiscale/fidelity data sources in Industry 4.0 is outlined.

Directly Printed Low-Cost Nanoparticle Sensor for Vibration Measurement during Milling Process.

A real-time, accurate, and reliable process monitoring is a basic and crucial enabler of intelligent manufacturing operation and digital twin applications. In this study, we represent a novel vibration measurement method for workpiece during the milling process using a low-cost nanoparticle vibration sensor. We directly printed the vibration sensor based on silver nanoparticles positioned onto a polyimide substrate using an aerodynamically-focused nanomaterials printing system, which is a direct printing technique for inorganic nanomaterials positioned onto a flexible substrate. Since it does not require any post-process such as chemical etching and heat treatment, a highly sensitive vibration sensor composed of a microscale porous structure was fabricated at a cost of several cents each. Furthermore, accurate and reliable vibration data was obtained by simple and direct attachment to a workpiece. In this study, we discussed the performance of vibration measurement of a fabricated sensor in comparison to a commercial vibration sensor. Using frequency and power spectrum analysis of obtained data, we directly measured the vibration of workpiece during the milling process, according to a process parameter. Lastly, we applied a fabricated sensor for the digital twins of turbine blade manufacturing in which vibration greatly affects the quality of the product to predict the process defects in real-time.

VascuTrainer: A Mobile and Disposable Bioreactor System for the Conditioning of Tissue-Engineered Vascular Grafts.

In vitro tissue engineering of vascular grafts requires dynamic conditioning in a bioreactor system for in vitro tissue maturation and remodeling to receive a mechanically adequate and hemocompatible implant. The goal of the current work was to develop a bioreactor system for the conditioning of vascular grafts which is (i) able to create a wide range of flow, pressure and frequency conditions, including physiological ones; (ii) compact and easy to assemble; (iii) transportable; (iv) disposable. The system is driven by a small centrifugal pump controlled via a custom-made control unit, which can also be operated on batteries to allow for autonomous transportation. To show the potential of the newly developed bioreactor system small-caliber vascular composite grafts (n = 5, internal diameter = 3 mm, length = 12.5 cm) were fabricated using a fibrin scaffold embedding human umbilical artery smooth muscle cells and a polyvinylidene fluoride warp-knitted macroporous mesh. Subsequently, the vascular grafts were endothelialized and mounted in the bioreactor system for conditioning. The conditioning parameters remained within the predefined range over the complete conditioning period and during operation on batteries as tested for up to 25 h. Fabrication and pre-conditioning under arterial pressure and shear stress conditions resulted in robust and hemocompatible tissue-engineered vascular grafts. Analysis of immunohistochemical stainings against extracellular matrix and cell-specific proteins revealed collagen I and collagen III deposition. The luminal surface was confluently covered with endothelial cells. The developed bioreactor system showed cytocompatibility and pH, pO2, pCO2, glucose and lactate stayed constant. Sterility was maintained during the complete fabrication process of the vascular grafts. The potential of a versatile and mobile system and its functionality by conditioning tissue-engineered vascular grafts under physiological pressure and flow conditions could be demonstrated.

New concepts and materials for the manufacturing of MR-compatible guide wires.

This paper shows the development of a new magnetic resonance imaging (MRI)-compatible guide wire made from fiber-reinforced plastics. The basic material of the developed guide wire is manufactured using a specially developed micro-pullwinding technology, which allows the adjustment of tensile, bending, and torsional stiffness independent from each other. Additionally, the micro-pullwinding technology provides the possibility to vary the stiffness along the length of the guide wire in a continuous process. With the possibilities of this technology, the mechanical properties of the guide wire were precisely adjusted for the intended usage in MRI-guided interventions. The performance of the guide wire regarding the mechanical properties was investigated. It could be shown, that the mechanical properties could be changed independently from each other by varying the process parameters. Especially, the torsional stiffness could be significantly improved with only a minor influence on bending and tensile properties. The precise influence of the variation of the winding angle on the mechanical and geometrical properties has to be further investigated. The usability of the guide wire as well as its visibility in MRI was investigated by radiologists. With the micro-pullwinding technology, a continuous manufacturing technique for highly stressable, MRI-safe profiles is available and can be the trigger for a new class of medical devices.

Environmental assessment of ester-based lubricants after application.

GOAL, SCOPE AND BACKGROUND: Lubricants based on renewable resources are an environmentally friendly alternative to petrochemical products due to their better ecotoxicological performance and their excellent biodegradability. To improve the technical performance of lubricants, and to reduce friction and wear, the use of additives is nowadays obligatory. The collaborative research center SFB 442 aims at developing environmentally acceptable lubricants that facilitate the avoidance of these additives by transferring their function to suitable coatings. For a complete assessment of the ecological performance of these newly developed lubricants, the whole life cycle including production, application as well as disposal and fate in the environment is studied. In the following study the focus was on the application and its influence on the environmental behavior of the lubricant. The application of lubricants leads, among other things, to the intake of metals due to abrasion from tools, work pieces or mechanical components. Previous examinations indicated a possible influence of metals on the toxicity of eluates prepared from used lubricants (Erlenkaemper et al. 2005). To clarify if the apparent toxicity of used lubricants solely results from the intake of metals, the extractability of these metals from the oil matrix is determined. By combining chemical analyses with bioassays, the bioavailability of metals that are present in the extract is estimated. To further investigate the relevance of metals on toxicity, toxic units (TU) were calculated and related to the results of the bioassays. Interactions between the metals were investigated with aqueous mixtures of metal chlorides and calculations based on the concept of concentration addition and independent action. METHODS: A lubricant mixture was applied to a tribological test bench that simulates real conditions of use and extremely short time load, respectively. Samples were taken at particular times, water soluble fractions (WSF) of these fluids were prepared and dilution series were investigated in several bioassays. Concentration of metals and total organic carbon (TOC) were determined in the eluates. TUs were calculated according to Sprague (1970) and mixture toxicity was calculated according to the concept of concentration addition (Loewe and Muischnek 1926) and independent action (Bliss 1939). RESULTS: Analyses of the metal content of the lubricant and the eluates clearly revealed the availability of the metals in the aqueous extracts. Especially copper, zinc, nickel and chromium were found and their concentrations increased during the time of use. The water extractable fraction, e.g., of copper, rose from 8.8% to 45.3% of the total content in the lubricant after 33.5 hours of use. Tests performed with the algal growth inhibition assay and the luminescence inhibition assay revealed the uptake or absorption by the organisms and, thus, the bioavailability of the metals. The calculation of TUs partly indicated a possible influence of the metals on ecotoxicity of the eluates. Copper reached concentrations equal to or higher than the EC50 value of copper chloride in the growth inhibition assays with algae and Ps. putida as well in the immobilization assay with daphnids. TUs for copper are also larger than 1 for the algal growth inhibition assay. The EL50 values indicated that the luminescence inhibition assay was the most sensitive test system, with values between 4.7% and 9.6%. While the toxicity towards algae and V. fischeri in the growth inhibition assay decreased until both organisms were no longer influenced by the exposure, the EL50 values for the D. magna immobilization assay and the Ps. putida growth inhibition assay decreased with the progressing use of the lubricant. The tested metal salt mixtures showed that Ps. putida, algae and daphnids are the most sensitive organisms with EC50 values below 1 mg/l. DISCUSSION: Although the intake of metals mainly occurred via abrasion of particles, the results revealed the availability of these metals in water. The availability varied for each of the four metals. For both the algal growth inhibition assay and the luminescence inhibition assay, an uptake or absorption of the metals could be demonstrated. The calculated TUs indicated an effect in some bioassays that was not verified in the test itself. The influence of copper on V. fischeri, for example, was not confirmed while the EL50 values for the daphnid bioassay decreased, meaning that the eluates became more toxic with progressing use of the lubricant. The calculations of mixture toxicity based on the concept of concentration addition demonstrated good correlations with the tested metal mixtures, but also a different sensitivity of the organisms. CONCLUSIONS: The results presented here reveal the availability of those metals in water that were taken in during the use of the lubricant in a tribological test bench and, thus, have the possibility of interacting with the organisms. The availability of the metals in the bioassays was proven by chemical analyses. The calculation of TUs and the corresponding EL50 values, however, indicate different availabilities of the metals. The results of the metal salt mixtures show good correlations with calculations of mixture toxicity based on concentration addition. Moreover, the varying sensitivity of the organisms when exposed to eluates or metal mixtures indicates a different bioavailability of the metals and/or the presence of other compounds that exert toxic action. RECOMMENDATIONS AND PERSPECTIVES: For further investigations, the organic oil matrix and its influence on the toxicity have to be taken into account. The toxicity of the eluates may not only be due to metals; additional effects could arise from changes in the lubricant itself.

Development of a compression molding process for three-dimensional tailored free-form glass optics.

Because of the limitation of manufacturing capability, free-form glass optics cannot be produced in a large volume using traditional processes such as grinding, lapping, and polishing. Very recently compression molding of glass optics became a viable manufacturing process for the high-volume production of precision glass optical components. An ultraprecision diamond-turning machine retrofitted with a fast tool servo was used to fabricate a free-form optical mold on a nickel-plated surface. A nonuniform rational B-spline trajectory generator was developed to calculate the computer numerical control machine tool path. A specially formulated glass with low transition temperature (Tg) was used, since the nickel alloy mold cannot withstand the high temperatures required for regular optical glasses. We describe the details of this process, from optical surface geometry, mold making, molding experiment, to lens measurement.