Fluid Dynamics in the HeartMate 3: Influence of the Artificial Pulse Feature and Residual Cardiac Pulsation

Ventricular assist devices (VADs), among which the HeartMate 3 (HM3) is the latest clinically approved representative, are often the therapy of choice for patients with end‐stage heart failure. Despite advances in the prevention of pump thrombosis, rates of stroke and bleeding remain high. These complications are attributed to the flow field within the VAD, among other factors. One of the HM3’s characteristic features is an artificial pulse that changes the rotor speed periodically by 4000 rpm, which is meant to reduce zones of recirculation and stasis. In this study, we investigated the effect of this speed modulation on the flow fields and stresses using high‐resolution computational fluid dynamics. To this end, we compared Eulerian and Lagrangian features of the flow fields during constant pump operation, during operation with the artificial pulse feature, and with the effect of the residual native cardiac cycle. We observed good washout in all investigated situations, which may explain the low incidence rates of pump thrombosis. The artificial pulse had no additional benefit on scalar washout performance, but it induced rapid variations in the flow velocity and its gradients. This may be relevant for the removal of deposits in the pump. Overall, we found that viscous stresses in the HM3 were lower than in other current VADs. However, the artificial pulse substantially increased turbulence, and thereby also total stresses, which may contribute to clinically observed issues related to hemocompatibility

3D printing of functional assemblies with integrated polymer-bonded magnets demonstrated with a prototype of a rotary blood pump

Conventional magnet manufacturing is a significant bottleneck in the development processes of products that use magnets, because every design adaption requires production steps with long lead times. Additive manufacturing of magnetic components delivers the opportunity to shift to agile and test-driven development in early prototyping stages, as well as new possibilities for complex designs. In an effort to simplify integration of magnetic components, the current work presents a method to directly print polymer-bonded hard magnets of arbitrary shape into thermoplastic parts by fused deposition modeling. This method was applied to an early prototype design of a rotary blood pump with magnetic bearing and magnetic drive coupling. Thermoplastics were compounded with 56 vol.% isotropic NdFeB powder to manufacture printable filament. With a powder loading of 56 vol.%, remanences of 350 mT and adequate mechanical flexibility for robust processability were achieved. This compound allowed us to print a prototype of a turbodynamic pump with integrated magnets in the impeller and housing in one piece on a low-cost, end-user 3D printer. Then, the magnetic components in the printed pump were fully magnetized in a pulsed Bitter coil. The pump impeller is driven by magnetic coupling to non-printed permanent magnets rotated by a brushless DC motor, resulting in a flow rate of 3 L/min at 1000 rpm. For the first time, an application of combined multi-material and magnet printing by fused deposition modeling was shown. The presented process significantly simplifies the prototyping of products that use magnets, such as rotary blood pumps, and opens the door for more complex and innovative designs. It will also help postpone the shift to conventional manufacturing methods to later phases of the development process

Killer-like receptors and GPR56 progressive expression defines cytokine production of human CD4+ memory T cells

All memory T cells mount an accelerated response on antigen reencounter, but significant functional heterogeneity is present within the respective memory T-cell subsets as defined by CCR7 and CD45RA expression, thereby warranting further stratification. Here we show that several surface markers, including KLRB1, KLRG1, GPR56, and KLRF1, help define low, high, or exhausted cytokine producers within human peripheral and intrahepatic CD4+ memory T-cell populations. Highest simultaneous production of TNF and IFN-γ is observed in KLRB1+KLRG1+GPR56+ CD4 T cells. By contrast, KLRF1 expression is associated with T-cell exhaustion and reduced TNF/IFN-γ production. Lastly, TCRβ repertoire analysis and in vitro differentiation support a regulated, progressive expression for these markers during CD4+ memory T-cell differentiation. Our results thus help refine the classification of human memory T cells to provide insights on inflammatory disease progression and immunotherapy development

Hydraulic Characteristics and Flow-field Related Hemocompatibility of Rotary Blood Pump Designs

Rotary blood pumps (RBPs) are implanted into patients with end-stage heart failure to support the left heart by pumping blood from the left ventricle to the aorta. Although the survival rate of patients supported with RBPs has increased substantially over the last decades, patients still suffer from a high incidence of adverse events such as infection, major bleeding or cerebral strokes. Many of these adverse events can be linked to the hemocompatibility of the RBP. And hemocompatibility, in turn, is closely related to the flow conditions in the RBP. The design of RBPs is based on the same principles as industrial turbomachinery. Whereas design rules and guidelines for turbomachinery design in industrial applications have been collected and refined over many decades, specific design knowledge for RBPs is rare and subjected to additional requirements different from industrial application. These requirements include the sufficient hemocompatibility of the pumps and the operation under dynamic conditions of the clinical application. Thus, this thesis aims to contribute to the design knowledge for RBPs in those two areas. The overall objective of this thesis is twofold: (I.) to model and compare the hydraulic behavior of RBPs under realistic pressure conditions of the cardiac cycle and (II.) to relate effects of typical RBP design parameters to indicators of hemocompatibility. In order to obtain repeatable and accurate in vitro experiments, a viscosity control was implemented into a mock circulation. The results of this thesis have implications for the design and testing of new RBPs, but also for the modeling and analysis procedures of existing RBPs. To investigate the hydraulic characteristics of implantable RBPs, an universal mathematical model of the static and dynamic hydraulic pump behavior was developed. This model was then used to systematically compare four current RBPs at clinically relevant, dynamic operating conditions. The model structure was based on principles of turbomachinery, including the low and backflow region, and it proved to be applicable to each of the investigated RBPs. The determined hydraulic behavior of the RBPs did not show any characteristic distinction between axial-flow and radial-flow pumps. For the simulated support conditions it was observed that the flow pulsatility varied greatly for the different RBPs and backflow occurred during partial support conditions for three out of the four RBPs. To investigate the influence of the design parameters of an RBP on hemocompatibility indicators, an RBP design was developed using industrial guidelines. Selected design parameters of this RBP design were varied systematically and the resulting effects on flow field and hydraulic performance were simulated using computational fluid dynamics. The flow fields were analyzed based on Eulerian and Lagrangian features, shear stress histograms and six indicators of hemocompatibility. Potentially damaging shear stress conditions were found for larger gap size and a higher number of blades. The extent of stagnation and recirculation zones was reduced with lower numbers of blades and a semi-open impeller, but it was increased with smaller clearance gaps. The Lagrangian hemolysis index showed a negative correlation with hydraulic efficiency and no correlation with the Eulerian threshold-based metric for hemolysis. In order to obtain repeatable and accurate in vitro experiments for the previously mentioned investigations, the control of the fluid viscosity was implemented in an existing mock circulation. This accounts for evaporation and temperature changes as well as for mimicking different viscosities of blood. The implemented viscosity control was then used for investigating an implantable RBP at different viscosities in the range of blood viscosities of patients with heart assist devices. For average support conditions, the influence on the measured head pressure was negligible, whereas the measured motor current deviated noticeably for higher speeds

A Taxonomy of Testing Activities in Product Development

We propose a taxonomy for categorizing testing activities on distinct levels with respect to the type of knowledge they are intended to provide. Our taxonomy adds to the well-established testing categories validation and verification the categories of experiment and trial-anderror. This theoretical model should help practitioners and educators to understand and explain different types of tests and to pass on knowledge

Linking Testing Activities with Success in Agile Development of Physical Products

Agile development methods are becoming increasingly important for mechanical engineering and the development of physical products. A key element of agile development and an integral part of the product development process is testing. This paper investigates the link between testing activities and success in agile product development. An observational study was conducted with 355 students grouped into 72 teams. Each team developed a physical product in a 12-week project. The project structure incorporated several aspects of the agile method Scrum. At the end of the project, the performance of each team’s product was evaluated with a performance score. During the project, the participants documented their invested time in development activities. To validate the result of the self-assessment, the usage of the mechatronic equipment of the individual teams was logged electronically for methodological triangulation. Statistical analysis was carried out using multiple regression models. The results show that time invested early in the project and testing activities throughout the project were statistically significant predictors of success. Furthermore, the results highlight the variety of performed testing activities and show that testing beyond the activities within Verification and Validation were performed until the very end of the project. The study results underline the importance of testing and support essential concepts discussed in the literature with quantitative empirical evidence.ISSN:2212-827

Fluid Dynamics in the HeartMate 3: Influence of the Artificial Pulse Feature and Residual Cardiac Pulsation

ISSN:1525-1594ISSN:0160-564

Fluid dynamics in the HeartMate 3: Influence of the artificial pulse feature and residual cardiac pulsation

ISSN:1525-1594ISSN:0160-564

3D Printing of Functional Assemblies with Integrated Polymer-Bonded Magnets Demonstrated with a Prototype of a Rotary Blood Pump

Conventional magnet manufacturing is a significant bottleneck in the development processes of products that use magnets, because every design adaption requires production steps with long lead times. Additive manufacturing of magnetic components delivers the opportunity to shift to agile and test-driven development in early prototyping stages, as well as new possibilities for complex designs. In an effort to simplify integration of magnetic components, the current work presents a method to directly print polymer-bonded hard magnets of arbitrary shape into thermoplastic parts by fused deposition modeling. This method was applied to an early prototype design of a rotary blood pump with magnetic bearing and magnetic drive coupling. Thermoplastics were compounded with 56 vol.% isotropic NdFeB powder to manufacture printable filament. With a powder loading of 56 vol.%, remanences of 350 mT and adequate mechanical flexibility for robust processability were achieved. This compound allowed us to print a prototype of a turbodynamic pump with integrated magnets in the impeller and housing in one piece on a low-cost, end-user 3D printer. Then, the magnetic components in the printed pump were fully magnetized in a pulsed Bitter coil. The pump impeller is driven by magnetic coupling to non-printed permanent magnets rotated by a brushless DC motor, resulting in a flow rate of 3 L/min at 1000 rpm. For the first time, an application of combined multi-material and magnet printing by fused deposition modeling was shown. The presented process significantly simplifies the prototyping of products that use magnets, such as rotary blood pumps, and opens the door for more complex and innovative designs. It will also help postpone the shift to conventional manufacturing methods to later phases of the development process