Testing & Simulation of Artificial Organs

Testing & Simulation Medical Device Development Need Design & Prototyping Preclinical Clinical Mechanical strength ______

Testing & Simulation Approval Launch Testing – what and how?Thrombogenicity Gas transfer Durability ______

Testing & Simulation Standards & Guidelines ISO: International Organization for ______ − DIN (German Institute for Standardization) participates as member

Device-specific standards − Cardiovascular implants - Cardiac valve prostheses – ISO 5840 − Cardiovascular implants and artificial organs - Blood-gas exchangers (oxygenators) – ISO 7199 − ______ - Active implantable medical devices – ISO 14708 ▪ Part 5: Circulatory support devices −…

Definition Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application Mandatory tests depend on − Nature of body contact (e.g.

Biological systems are highly complex ➔ Impossible to understand w/o ______

Virtual exploration of many scenarios ➔ Impossible to do ______/in vivo

Mechanistic understanding of a system ➔ Therapies, devices etc. Regulatory pipeline medical devices 44 Testing & ______

Hemocompatibility tests are challenging but provide lots of information about blood-material ______

In-vitro tests reduce ______ trials

Testing is highly important for artificial organs and any medical ______

The duration of contact for biocompatibility testing can be limited (≤ 24 h), prolonged (24 h – 30 d), or ______ (> 30 d)

The interaction of blood components with artificial material is a key aspect of ______

Hemolysis leads to the destruction of red blood cells and the release of cell ______ hemoglobin

The '3R' principle in pre-clinical animal trials stands for Replace, ______, Refine

Hemodynamic testing assesses the impact of high shear rates, regions of stasis & turbulences, and ______

The cardiovascular implants and artificial organs standard ISO 5840 is specific to cardiac valve ______

The efficiency of a blood pump is measured using the formula: Efficiency = Power/Flow × ______

Blood pump hemolysis can be assessed using the Normalized Index of Hemolysis (NIH) and the Modified Index of ______

Biocompatibility testing includes evaluation of cytotoxicity, sensitization, irritation, and material-related ______

Biological systems are highly complex ➔ Impossible to understand w/o ______

Virtual exploration of many scenarios ➔ Impossible to do in vitro/in ______

Mechanistic understanding of a system ➔ Therapies, devices etc. Regulatory pipeline medical devices 44 Testing & ______

The interaction of blood components with artificial material is a key aspect of ______

Testing is highly important for artificial organs and any medical ______

Modeling, Discretization, and Iterative solutions are used to compute CFD Flow field numerically by ______

Results of CFD Flow field computation are strongly dependent on ______ conditions

Spatial and temporal resolution, including mesh and timestep, are important for the ______ model

Validation and verification are ______ for the development of CFD Flow field computation

George E.P.Box cleverly said, “All models are wrong, but some are ______”

The interaction of blood components with artificial material is a key aspect of ______

Mechanical strength ______

Durability ______

The duration of contact for biocompatibility testing can be limited (≤ 24 h), prolonged (24 h – 30 d), or ______ (> 30 d)

Hemodynamic testing assesses the impact of high shear rates, regions of stasis & turbulences, and ______

CFD stands for Computational ______ Dynamics

Turbulence in flow: chaotic changes in pressure/velocity caused by disturbance of the flow field laminar ➔ transitional ➔ turbulent ______ (eddies) on various spatial scales big ➔ smaller ➔ smallest ➔ heat turbulent free jet (CFD Calculation)

The cardiovascular implants and artificial organs standard ISO 5840 is specific to cardiac valve ______

The '3R' principle in pre-clinical animal trials stands for Replace, ______, Refine

The duration of contact for biocompatibility testing can be limited (≤ 24 h), prolonged (24 h – 30 d), or ______ (> 30 d)

The interaction of blood components with artificial material is a key aspect of ______

Results of CFD Flow field computation are strongly dependent on ______ conditions

The efficiency of a blood pump is measured using the formula: Efficiency = Power/Flow × ______

Hemolysis leads to the destruction of red blood cells and the release of cell ______ hemoglobin

Hemodynamic testing assesses the impact of high shear rates, regions of stasis & turbulences, and ______

Mesh resolution may affect the entire flow field. Unrealistic velocity distribution. Development of vortices in wake region. Even “simple” numerical setups might be more intriguing than you think. ______ Fine Flow through squeezed tube

Mesh strongly influences the results of the simulation. Important step in the verification process. Know what output is of interest for you. Gradient based outputs (shear stresses) need very fine ______

Recall of CFD theory 1st step: Modeling ✓ 2nd step: Discretization ✓ 3rd step: ______

Errors/assumptions along the pipeline affect our result. Solution errors: Equations are solved numerically ➔ Are just approximations!!! Mathematical algorithms to solve the system of equations (PDE) Use convergence plots to see if solution algorithm “works” Not ______?

Results of CFD Flow field computation are strongly dependent on ______ conditions. Hemodynamic testing assesses the impact of high shear rates, regions of stasis & turbulences, and ______

Rotational velocity (top), absolute velocity (bottom).Ψ/Φ: Dimensionless numbers pressure/flow 54 Testing & Simulation Example I: CFD based design optimization Homogeneous velocity distribution Stagnation area prone to thrombus formation High velocities at blade outlets Initial and modified design of an RBP and its effect on velocity and ______

Reduction of ______ rates Example I: Parameter based design exploration β1 β2 many variations in β1 and β2 Parameter based design exploration.left: initial design, center: meta-model, right: optimal design

FDA Round Robin initiative – Let’s test CFD/PIV around the world FDA Round Robin Pump curve/pressure head ➔ hydraulic vs.CFD Velocity distribution ➔ PIV vs.CFD Hemolysis ➔ in-vitro blood vs. ______

The '3R' principle in pre-clinical animal trials stands for Replace, ______, Refine

Validation and verification are ______ for the development of CFD Flow field computation

Spatial and temporal resolution, including mesh and timestep, are important for the ______ model

The efficiency of a blood pump is measured using the formula: Efficiency = Power/Flow × ______

The duration of contact for biocompatibility testing can be limited (≤ 24 h), prolonged (24 h – 30 d), or ______ (> 30 d)

Results of CFD Flow field computation are strongly dependent on ______ conditions

Modeling, Discretization, and Iterative solutions are used to compute CFD Flow field numerically by ______