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Published on: January 31, 2018
Magnetic fluorescent microparticles as markers for particle transfer in extracorporeal blood purification
Marion Ettenauer1, Thomas Posnicek, Martin Brandl
1Center for Biomedical Technology, Danube University Krems, Austria.
Abstract:
The microspheres-based detoxification system (MDS) is a combined membrane-adsorption system for extracorporeal blood purification in which adsorbent microparticles are recirculated in an extracorporeal filtrate circuit. Because the plasma filter represents the only barrier between the adsorbents and the patient's blood, there is the potential risk of particle entrance into the patient in case of a membrane rupture. To guarantee first fault safety of the system required for clinical application, magnetic fluorescent microparticles are added as markers to the adsorbent circuit. Detection of these particles in the venous blood line results in immediate shutdown of the pumps. Magnetic beads were functionalized with cresyl violet and tested with an in vitro setup of the particle detector to assess the detection limit in different matrices (water versus blood) as well as the influence of flow rate and particle size on the signal. In addition, biocompatibility and influence of sterilization on the performance of the particles were assessed. Functionalization of the magnetic particles with cresyl violet yielded fluorescent particles that were stable at 4 degrees C for at least 12 months. No leakage of dye was detectable, and the particles were neither cytotoxic nor mutagenic. The particles could be steam sterilized without significant loss in fluorescence intensity. With an in vitro setup of the particle detector, 0.1 mg and 5 mg of particles were reproducibly detectable in water and blood, respectively.
Insights
Magnetic fluorescent microparticles ensure safety in extracorporeal blood purification systems. These particles detect potential adsorbent leakage, triggering an immediate system shutdown to protect patients.
Area of Science:
- Biomedical Engineering
- Materials Science
- Toxicology
Background:
- The microspheres-based detoxification system (MDS) utilizes adsorbent microparticles for extracorporeal blood purification.
- A critical safety concern is the potential for microparticle leakage into patient blood if the plasma filter membrane ruptures.
Purpose of the Study:
- To develop and evaluate magnetic fluorescent microparticles as safety markers for the MDS.
- To assess the detection limits, stability, biocompatibility, and sterilization effects on these marker particles.
Main Methods:
- Magnetic beads were functionalized with cresyl violet to create fluorescent markers.
- An in vitro particle detector setup was used to test detection limits in water and blood under varying flow rates and particle sizes.
- Biocompatibility (cytotoxicity, mutagenicity) and sterilization effects (steam sterilization) were evaluated.
Main Results:
- Fluorescent particles demonstrated stability for over 12 months at 4°C with no detectable dye leakage.
- Particles were found to be neither cytotoxic nor mutagenic.
- Steam sterilization did not significantly impact fluorescence intensity.
- Detection limits were established at 0.1 mg in water and 5 mg in blood.
Conclusions:
- Magnetic fluorescent microparticles are suitable safety markers for the MDS, ensuring first-fault safety.
- The developed marker particles exhibit excellent stability, biocompatibility, and resistance to sterilization.
- The particle detection system reliably identifies potential leaks, enabling prompt system shutdown.

