Design, verification and validation of a novel large-volume production of ghost cells

  • Konstruktion, Verifizierung und Validierung einer neuartigen Großmengenproduktion von Ghost Cells

Schöps, Malte; Steinseifer, Ulrich (Thesis advisor); Jupke, Andreas (Thesis advisor)

Düren : Shaker Verlag (2022)
Book, Dissertation / PhD Thesis

In: Aachener Beiträge zur Medizintechnik 68
Page(s)/Article-Nr.: XI, 122 Seiten : Illustrationen, Diagramme

Dissertation, RWTH Aachen University, 2021


(1) Mechanical circulatory support is mainly based on moving actuators in the organism blood, such as the blades of centrifugal blood pumps. Using these devices in the treatment of patients exposes blood to unusual stress, causing hemolysis. Hemolysis is still one of the major challenges in the development of mechanical circulatory support devices, apart from thrombocyte activation. Close to the surface between rotor and blood, high shear stress acts on red blood cells. As soon as shear stress exceeds a threshold value, it leads to hemolysis, destroying red blood cells by rupturing their membranes. (2) The fluorescent hemolysis detection method (FHDM) developed by Jansen et al. investigates hemolysis in more detail. With this method, a spatial resolution of hemolysis hotspots is realized based on ghost cells. Ghost cells are red blood cells with reduced intracellular hemoglobin. The FHDM is limited by the small amounts of ghost cells produced. Larger volumes would allow to perform this method even according to international standards and on real size models of mechanical circulatory support systems. The aim of this study was to develop a process engineering system using semi-automatic mechatronic technology to increase ghost cell production volume. (3) Until now, production volume was limited to 10.3 mL of ghost cells with a hematocrit of 30 % due to predominantly manual process steps. By implementation of a novel semi-automated large-volume batch production system (LVBPS) in the existing method, productivity was increased 22-fold while multiplying process efficiency by 34 times. Time-consuming manual work such as pipetting was supported by sensor-based process engineering. In addition to increased efficiency, process monitoring was implemented in the system to ensure consistent process parameters and semi-automation of the production process. Moreover, the properties of ghost cells as blood substitute such as rheology and deformability were maintained or even enhanced compared to manual production. With the help of the LVBPS, the objective of producing large volumes of ghost cells was successfully achieved.