TY - JOUR
T1 - Regional heparinization via simultaneous separation and reaction in a novel Taylor-Couette flow device
AU - Ameer, G. A.
AU - Raghavan, S.
AU - Sasisekharan, R.
AU - Harmon, W.
AU - Cooney, C. L.
AU - Langer, R.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/6/5
Y1 - 1999/6/5
N2 - The development of a safe and efficient bioreactor design has remained a challenge for the clinical application of immobilized enzymes. Specifically, the use of immobilized heparinase I has been the target of many studies to make heparin anticoagulation therapy safer for the critically ill patient with kidney failure or heart disease. We have investigated the use of Taylor- Couette flow for a novel type of bioreactor. In a previous study, we showed that the fluidization of agarose immobilized heparinase within Taylor vortices in whole blood can lead to extensive blood damage in the form of cell depletion and hemolysis. Based on these findings, we designed and developed a reactor, referred to as vortexflow plasmapheretic reactor (VFPR), that incorporated plasmapheresis and fluidization of the agarose in the reactive compartment, separate from the whole-blood path. In the present study, immobilized heparinase I was tested as a means of achieving regional heparinization of a closed circuit. This is a method in which heparin is infused into the extracorporeal circuit predialyzer and neutralized postdialyzer. Saline studies were performed with an immobilized heparinase I- packed bed and with the VFPR. An in vitro feasibility study was performed with the VFPR using human blood. The VFPR achieved heparin conversions of 44 ± 0.5% and 34 ± 2% in saline and blood, respectively. In addition, the VFPR caused no blood damage. We report a novel method to achieve fluidization which depended on secondary, circumferencial flow, and was independent of the primary flow through the device.
AB - The development of a safe and efficient bioreactor design has remained a challenge for the clinical application of immobilized enzymes. Specifically, the use of immobilized heparinase I has been the target of many studies to make heparin anticoagulation therapy safer for the critically ill patient with kidney failure or heart disease. We have investigated the use of Taylor- Couette flow for a novel type of bioreactor. In a previous study, we showed that the fluidization of agarose immobilized heparinase within Taylor vortices in whole blood can lead to extensive blood damage in the form of cell depletion and hemolysis. Based on these findings, we designed and developed a reactor, referred to as vortexflow plasmapheretic reactor (VFPR), that incorporated plasmapheresis and fluidization of the agarose in the reactive compartment, separate from the whole-blood path. In the present study, immobilized heparinase I was tested as a means of achieving regional heparinization of a closed circuit. This is a method in which heparin is infused into the extracorporeal circuit predialyzer and neutralized postdialyzer. Saline studies were performed with an immobilized heparinase I- packed bed and with the VFPR. An in vitro feasibility study was performed with the VFPR using human blood. The VFPR achieved heparin conversions of 44 ± 0.5% and 34 ± 2% in saline and blood, respectively. In addition, the VFPR caused no blood damage. We report a novel method to achieve fluidization which depended on secondary, circumferencial flow, and was independent of the primary flow through the device.
KW - Agarose bioreactor
KW - Blood detoxification
KW - Fluidized bed
KW - Heparin neutralization
KW - Heparinase
KW - Taylor-Couette flow
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U2 - 10.1002/(SICI)1097-0290(19990605)63:5<618::AID-BIT12>3.0.CO;2-3
DO - 10.1002/(SICI)1097-0290(19990605)63:5<618::AID-BIT12>3.0.CO;2-3
M3 - Article
C2 - 10397818
AN - SCOPUS:0033526548
SN - 0006-3592
VL - 63
SP - 618
EP - 624
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
IS - 5
ER -