Dynamic Nuclear Polarization Polarizer for Sterile Use Intent

Dynamic Nuclear Polarization Polarizer for Sterile Use Intent
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DOI:
10.1002/nbm.1682
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发表时间:
2011-10-01
期刊:
影响因子:
2.9
通讯作者:
Skloss, Timothy W.
Skloss, Timothy W.
中科院分区:
医学3区
文献类型:
--
作者:
Ardenkjaer-Larsen, Jan H.;Leach, Andrew M.;Skloss, Timothy W.

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设计、制作并测试了一种基于溶解动态核极化(DNP)方法的新型偏振器。偏振器与先前描述的偏振器不同,其设计具有无菌使用目的,并且与临床使用兼容。主要特点是:(1)包含构成无菌屏障的所有药物的整体一次性流体路径,(2)设计用于消除液体冷冻剂消耗的闭合循环低温系统,以及(3)多样品极化以增加通量。流体路径由装有待极化试剂的小瓶、分别连接到装有溶出介质的注射器的一对同心入口管和出口管以及接收器组成。流体路径可以在高达400 K和2.0 MPa的条件下运行,并产生高达100 mL的体积。在[1-(13)C]丙酮酸盐的情况下,在线过滤器将最终产品中的电子顺磁剂的量去除超过100倍。该系统使用的吸附泵与传统的低温制冷机。该系统通过泵送至低温和吸附泵再生的循环进行操作。磁体可同时容纳四个样品。在液氦体积为2.4 L的情况下,在68 h内(无样品热负荷)达到低于1 K的温度。液氦的再生可以在不到10 h内完成,并且在不到90 min内实现到冷态(< 1.2 K)的转变。仅用10 mW的微波功率就获得了36 +/- 4%的[1-(13)C]维生素C酸的固态极化。通过在15 min内引入样品,样品的加载向氦浴中增加了小于50 J的热量。溶解过程中施加在氦浴上的热负荷小于70 J。测得的液态极化为18 +/-2%。版权所有(C)2011约翰威利父子有限公司
A novel polarizer based on the dissolution-dynamic nuclear polarization (DNP) method has been designed, built and tested. The polarizer differs from those previously described by being designed with sterile use intent and being compatible with clinical use. The main features are: (1) an integral, disposable fluid path containing all pharmaceuticals constituting a sterile barrier, (2) a closed-cycle cryogenic system designed to eliminate consumption of liquid cryogens and (3) multi-sample polarization to increase throughput. The fluid path consists of a vial with the agent to be polarized, a pair of concentric inlet and outlet tubes connected to a syringe with dissolution medium and a receiver, respectively. The fluid path can operate at up to 400 K and 2.0 MPa and generates volumes as high as 100 mL. An inline filter removes the amount of electron paramagnetic agent in the final product by more than 100-fold in the case of [1-(13)C]pyruvate. The system uses a sorption pump in conjunction with a conventional cryocooler. The system operates through cycles of pumping to low temperature and regeneration of the sorption pump. The magnet accommodates four samples at the same time. A temperature of less than 1 K was achieved for 68 h (no sample heat loads) with a liquid helium volume of 2.4 L. The regeneration of the liquid helium could be achieved in less than 10 h, and the transition to cold (< 1.2 K) was achieved in less than 90 min. A solid state polarization of 36 +/- 4% for [1-(13)C]pyruvic acid was obtained with only 10 mW of microwave power. The loading of a sample adds less than 50 J of heat to the helium bath by introducing the sample over 15 min. The heat load imposed on the helium bath during dissolution was less than 70 J. The measured liquid state polarization was 18 +/- 2%. Copyright (C) 2011 John Wiley & Sons, Ltd.