Theoretical and experimental analysis of anti-A antibody capture in novel integrated bead and hollow fiber modules.

Theoretical and experimental analysis of anti-A antibody capture in novel integrated bead and hollow fiber modules.
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新型集成珠和中空纤维模块中抗 A 抗体捕获的理论和实验分析。

DOI:
10.1007/s10439-010-0233-x
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发表时间:
2011
影响因子:
3.8
通讯作者:
Federspiel,WilliamJ
Federspiel,WilliamJ
中科院分区:
工程技术2区
文献类型:
--
作者:
Alikhani,Azadeh;Federspiel,WilliamJ

文献摘要

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从血液中去除抗A/B抗体可降低ABO血型不合移植后超急性排斥反应的风险我们正在开发一种集成珠和纤维模块(BSAF),可选择性地从血液中去除抗A抗体。在BSAF中,血液流过微滤纤维的内腔。Starling流将血浆从内部纤维腔运送到壳隔室中的珠粒,在壳隔室中抗体与珠粒上共价连接的抗原结合。在这项研究中,我们开发了一个数学模型,以指导临床BSAF设备的关键设计和操作参数的选择。该模型表明,对于给定的流速和储液器体积,抗体去除速率取决于集总参数kLmB/Qs的大小,该参数表征了微珠的抗体摄取速率与器械中Starling流速的比值。当kLmB/Qs→ 10时,预测灌注限制方案的最高抗体去除率;一旦获得该最大限度,则抗体去除率的任何进一步增加仅可通过增加流速来实现。关键模型预测在一系列实验中得到验证。然后使用该模型在概念上设计能够达到临床相关抗A清除率的BSAF。
Anti-A/B antibody removal from blood reduces the hyperacute rejection risk following ABO-incompatible transplantation. We are developing an integrated bead and fiber module (BSAF) that selectively removes anti-A from blood. In BSAF blood flows through the inner lumen of microfiltration fibers. Starling flow carries plasma from the inner fiber lumen to the beads in the shell compartment where antibodies bind to covalently attached antigens on the beads. In this study, we developed a mathematical model to guide the choice of key design and operational parameters for a clinical BSAF device. The model demonstrated that for a given flow rate and reservoir volume, antibody removal rate was dependent on the magnitude of a lumped parameter,kLmB/Qs, that characterizes the ratio of antibody uptake rate by the beads to the Starling flow rate in the device. The highest antibody removal rate was predicted for the perfusion limited regime, whenkLmB/Qs→ 10; Once this maximum limit was obtained, any further increase in the antibody removal rate was only possible by increasing the flow rate. Key model predictions were validated in a series of experiments. The model was then used to conceptually design a BSAF capable of a clinically relevant rate of anti-A removal.