Investigation of a whole blood fluidized bed Taylor-Couette flow device for enzymatic heparin neutralization

G. A. Ameer, W. Harmon, R. Sasisekharan, R. Langer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The use of clinical bioreactors will increase as more therapeutic proteins are being cloned, expressed, and produced at a reduced cost. The proposed use of an immobilized heparinase I reactor to make heparin anticoagulation a safer therapy is an example of how the specificity and high activity of an enzyme could be incorporated into a system to ultimately benefit a patient. However, the development of a safe and efficient bioreactor is important for the use of immobilized heparinase I and other therapeutic proteins designed for use in medical extracorporeal procedures. This study examined the possibility of using Taylor-Couette flow and 'flow- induced' recirculation of the agarose beads as a way to fluidize agarose- bound heparinase in whole blood. Heparinase I was immobilized onto agarose beads via cyanogen bromide activation. A reactor based on Taylor-Couette flow was designed and modified with a tangential recirculation line. The reactor was tested for efficacy and safety in vitro in human blood. Visualization studies in water and 42% glycerol were used to determine the minimum rotation rate for efficient fluidization. The strategic placement of the recirculation line allowed recirculation of the agarose without the use of an external pump. The device removed 90% of the heparin activity within 2 min from 450 cc of human blood at a blood flow rate of 100 mL/min. Furthermore, the device maintained inlet and outlet clotting times of 269 ± 10 and 235 ± 6 s, respectively, demonstrating the potential for regional heparinization. Blood damage was a function of gel volume fraction and rotation rate of the inner cylinder. Hemolysis of the red cells is an important issue when Taylor vortices are combined with macroscopic solid particles such as agarose beads. A modified Taylor-Couette flow device was developed to treat whole blood and operational criteria were established to minimize hemolysis.

Original languageEnglish (US)
Pages (from-to)602-608
Number of pages7
JournalBiotechnology and Bioengineering
Issue number5
StatePublished - Feb 20 1999


  • Agarose bioreactor
  • Detoxification of whole blood
  • Fluidized bed
  • Heparin neutralization
  • Heparinase
  • Taylor-Couette flow

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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