KBKanzler Biologicals
ENDE

Preclinical validation file

Research and validation

Development questions before medical claims. This page documents what must be tested for the modular artificial-heart concept before any defensible preclinical statement exists.

Validation matrix

Risk, method and open evidence are separated deliberately.

FieldRiskMethodOpen evidence
HemocompatibilityHemolysis, thrombus formation, platelet activation.Blood/surrogate loops, microscopy, deposits, markers.Long-duration evidence in assembled blood path.
Pulmonary pulsatilityToo little pulsatility or harmful pressure peaks.Pressure waves, pulse volume, frequency and compliance testing.Useful pulse envelope without unsafe peaks.
Thermal safetyHeating from pump, BMS or charging.Thermal maps, load cycles and tissue-phantom tests.Safe temperature limits under continuous operation.
Sensor plausibilityWrong response caused by drift or fouling.Fault injection and cross-sensor logic.Rules for contradictions between pressure, flow, rpm and temperature.

R-01 to R-18

Specific research clusters

Each cluster is an individual validation problem, not a repeated placeholder.

R-01Hemocompatibility

Hemocompatibility

Blood contact is the primary biological risk. The membrane surface, pump chamber, valve paths and microaxial pump flow path must be assessed as an assembled hydraulic path, not only as isolated materials. The pressure plate is not a blood-contacting element and should not be described as one.

Testing has to look for hemolysis, platelet activation, thrombus deposition, protein build-up and changes after endurance operation. The geometry must be checked for high-shear regions and low-washout pockets.

Open validation requirement: define markers, loop conditions, exposure time and acceptance limits before claiming blood compatibility.
R-02Shear forces

Shear forces

Shear is not a single number. It depends on rotor clearance, valve jets, membrane deformation, sudden area changes and bypass junctions. Short high-shear bursts and longer moderate shear exposure both matter.

CFD can indicate where shear may occur, but bench tests and hemolysis markers must confirm whether the predicted zones create damage.

Open validation requirement: connect CFD shear maps with measured hemolysis and pressure-flow data.
R-03Residence time and stagnation

Residence time and stagnation

Residence time determines how long blood remains in low-motion regions. In this concept the risk areas are chamber corners, membrane edge zones, valve pockets, bypass branches and the pulse chamber during partial filling.

Good average flow can still hide stagnant pockets. PIV or dye studies should show whether each cycle refreshes the chamber volume and whether bypass branches are washed out.

Open validation requirement: show washout behaviour for normal, pulse and bypass states.
R-04Thrombosis risk

Thrombosis risk

Thrombosis risk emerges from surface chemistry, shear history, stagnation and foreign-body response. It cannot be solved by a single material choice.

The validation plan should inspect surfaces after operation, record deposits by location, and compare results across flow states, temperatures and anticoagulated test conditions.

Open validation requirement: map deposit location and relate it to geometry and flow state.
R-05Pulmonary pulsatility

Pulmonary pulsatility

The pulmonary pump provides baseline continuous flow. The pulse chamber adds pressure and flow impulses and can also work as a buffer during bypass. The question is not whether pulses can be generated, but which pulse envelope is useful and not harmful.

Testing must vary frequency, volume, rise time, decay time and downstream compliance. The pulse chamber should not create brutal peaks simply to look physiological.

Open validation requirement: define safe pulse amplitude, frequency and volume ranges.
R-06Membrane fatigue

Membrane fatigue

The systemic membrane is cyclically loaded by the pressure plate. Fatigue may start at clamped edges, high-curvature regions or repeated contact zones.

Endurance testing must include stroke count, pressure load, temperature, membrane inspection and leakage checks. Short-cycle demonstrations are not durability evidence.

Open validation requirement: produce cycle-life data across realistic pressure loads.
R-07Valve life and timing

Valve life and timing

Inlet and outlet valves determine filling, ejection and backflow. A small timing error can create regurgitation, high shear or incomplete chamber emptying.

Bench tests should record opening pressure, closure behaviour, leakage, partial obstruction and deposit effects after repeated operation.

Open validation requirement: verify valve timing and leakage after endurance cycles.
R-08Rotor and bearing safety

Rotor and bearing safety

The microaxial pump may be small, but rotor and bearing behaviour decide heat, vibration, hemolysis and reliability. A normal rpm signal does not prove normal flow.

The pump must be tested for rpm-flow-pressure plausibility, temperature rise, obstruction response, vibration and bearing wear.

Open validation requirement: prove safe response when rotor speed and measured flow disagree.
R-09Particle management

Particle management

Mechanical drives, bearings, seals and guides can generate particles. Blood-contacting paths and lubricated drive regions must be separated.

Particle capture by filters or magnetic concepts is only a concept until particle size, material and capture efficiency are measured.

Open validation requirement: measure particle generation and containment after mechanical endurance.
R-10Thermal safety

Thermal safety

Heat can come from the pump, motor drive, control electronics, battery, BMS and inductive charging. In an implantable housing, heat dissipation is limited.

Thermal testing must combine continuous pump load, intermittent drive peaks, charging and tissue-like boundary conditions.

Open validation requirement: map temperature during combined operation and charging.
R-11Battery and BMS

Battery and BMS

The energy system has steady loads and peak loads. Continuous pulmonary pumping is different from high-force systemic actuation, and the BMS must protect both normal and fault states.

Validation should cover cell monitoring, overcurrent, deep discharge, balancing, thermal cutoffs, reserve mode and ageing.

Open validation requirement: define reserve behaviour after cell imbalance, ageing and high-load events.
R-12Inductive charging

Inductive charging

The 3-coil concept is meant to improve coupling tolerance and heat control, but this must be measured. Alignment error can turn electrical transfer into a thermal problem.

Testing should vary distance, lateral offset, angle, transferred power and charge duration using tissue-equivalent phantoms.

Open validation requirement: define safe charge windows and stop criteria.
R-13Sensor plausibility

Sensor plausibility

Single sensors fail, drift or become fouled. The controller must compare pressure, flow, rpm, temperature, valve state and chamber pressure instead of trusting one value.

Contradictions such as high rpm with low flow, rising pressure with falling flow, or unchanged pressure after valve command must trigger defined responses.

Open validation requirement: write and test plausibility rules for contradictory sensor states.
R-14Fault logic

Fault logic

The fault architecture should not jump from normal operation to panic. It needs staged responses: reduce power, bypass 1, bypass 2, alarm and conservative mode.

Fault injection must include blocked outlet, low inlet volume, valve sticking, sensor drift, pump heating and pulse chamber overpressure.

Open validation requirement: verify staged transitions under defined fault injection.
R-15CFD

CFD

CFD helps find candidate high-shear, recirculation and pressure-loss regions. It is not final proof because the result depends on mesh, boundary conditions and moving-wall assumptions.

The best use of CFD is to guide where PIV and bench sensors should look. Simulation-only results must remain labelled as simulation.

Open validation requirement: link CFD predictions to measured data instead of treating them as proof.
R-16PIV and flow visualization

PIV and flow visualization

PIV, dye tests or transparent models can reveal dead zones and jets that average flow sensors miss. They are especially useful around valves, membrane edges, bypass branches and pump inlets.

The method should be documented with fluid model, frame rate, geometry and operating state so that the visual result can be repeated.

Open validation requirement: show flow fields for normal, pulse and bypass operation.
R-17Bench tests

Bench tests

Bench testing must couple pressure, flow, compliance, resistance, temperature, rpm, valve state, particle data and hemolysis markers. A friendly single operating point is not enough.

Acceptance criteria should be defined before interpretation. Otherwise the same data can be overclaimed after the fact.

Open validation requirement: define pass/fail criteria before running validation tests.
R-18Regulatory evidence path

Regulatory evidence path

The path toward any medical-device claim would require material validation, sterilisation strategy, biocompatibility, hemocompatibility, electrical safety, software validation, risk management and long-duration evidence.

No page should imply clinical use or approval before those steps exist. The research page should openly separate concept, simulation, bench observation and validated evidence.

Open validation requirement: maintain traceability from hazard to control to verification evidence.