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Designing a Well-Mixed Heparinase Reactor Using Taylor Vortices for Bead Fluidization

This paper explores the use of Taylor Vortices to achieve a well-mixed state in a heparinase reactor with immobilized enzymes. Factors such as gap space and rotation rate of the inner cylinder were studied, and results showed successful immobilization of the enzyme with minimal leaching. The design also aimed to minimize blood damage by reducing hemolysis. A subsequent paper presents an improved design that simultaneously separates plasma and facilitates the enzyme reaction while treating whole blood at high flowrates, with reduced hemolysis.

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Designing a Well-Mixed Heparinase Reactor Using Taylor Vortices for Bead Fluidization

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  1. So if we were designing a heparinase reactor how would we get the beads containing the immobilized enzyme in a well-mixed state? The paper by Langer’s group, ie. Ameer et al. 1999 (I) looked at fluidization of whole blood in a Taylor-Couette Flow Device The Taylor vortices would facilitate the fluidization of the agarose beads and lead to a well-mixed reactor Taylor vortices are flow instabilities that occur within an annular gap of concentric cylinders when the inner cylinder is rotated above a critical rotation rate

  2. Factors affecting the fluidization of the beads included: • Gap space, 3.2 mm and 6.4 mm • Rotation rate of inner cylinder • Flow rate of blood thru the device

  3. Results and Discussion • Immobilization bound 95% of the soluble enzyme and retained 30-40% of the enzyme activity 2. Over a 4 day period of operation no leaching of the enzyme from the agarose was detected 3. Heparin degradation products were found to be nontoxic at [ ]’s up to 100x’s the expected levels during clinical exposure 4. Phase I clinical trials in healthy volunteers showed no acute reactions when exposed to soluble heparinase which was obtained from Flavobacterium heparinum

  4. Narrow gap 90% removal of heparin in 3 minutes

  5. Attempted to reduce blood damage in this initial design by: • Increasing the gap width while maintaining annular volume constant • Reducing the rotation rate Note that conversion is now about 80% at 3 minutes

  6. Note that Hb release is significantly reduced between design I and design II

  7. Blood cell damage reduced from design I to design II

  8. Constant flow showed about a 23% per pass removal Clinical application needs about 45%

  9. Although Taylor vortices are usually gentle to RBC’s this study showed that when used in combination with the agarose beads hemolysis of the RBC’s is a big problem. So, how would you solve this problem? The next paper by the same group and labelled II illustrates how they attacked this problem Design criteria: • efficacy, need a 40-50% per pass heparin conversion • Safety, no significant effect on whole blood cells, no hemolysis, no reduction in platelets or white blood cells, and no activation of these cells either 3. stability, stable operation at flowrates up to 300 ml/min 4. simplicity, simple operation and low cost To minimize blood damage, a device that SIMULTANEOUSLY effected plasma separation and the enzyme reaction with the capacity to treat whole blood at high flowrates was designed.

  10. Previous paper Poor mass transfer and loading issues Blood cells and the platelets would not come into contact with the agarose beads and hence minimize hemolysis

  11. Conversion about 34% and below their target of 40-50%, but could be increased by adding more beads

  12. Eliminating contact between the cells and the agarose beads as in this design was an effective way to significantly reduce hemolysis.

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