Scale Up of Hyperpolarized Xe Production

描述(申请人提供)：超极化氙气-129(HXE)MRI已被证明对肺的功能诊断成像具有极高的灵敏度，可能是技术上最有前途和商业上最可行的技术。肺健康的全面表征可能受益于多达8种不同的多升方案，理想情况下应在1小时内完成。三年前，我们团队发现了一种有效的极化方法，并开发了一种利用高流量、低压力极化机制的设备，在50%的速度下将产量提高了十多倍至1 L/小时。在我们的第一阶段方案中，我们认为，在假设温度、压力、激光照度和电池几何条件相似的情况下，将偏振器与几个并行工作的导热通道组装在一起，将允许按通道数量的一倍进行放大。此外，如果激光光谱可以变窄，那么将压力降低两倍可以使生产率再提高两倍。在第一阶段，我们开发了新的制造技术，组装了一个铜原型，调整了我们现有的激光和磁性基础设施以安装它，并对其性能进行了表征。我们证实了预测，多通道偏振器柱以每百瓦窄激光功率每小时两升的速度提供&gt；50%的偏振HXE，最高可达250瓦，比我们以前的世界最佳生产率提高了六倍。我们发现，一些激光元件中的热应力引起的双折射正在危及我们的铜柱技术的偏振演示，直到可用的激光功率达到全千瓦，这个问题现在可以很容易地纠正。在第二阶段，我们建议对我们的新原型偏振器进行全面的表征，展示出氙气偏振器的生产产量扩大了20倍。我们将在混合气体、压力、温度、流速和激光功率的广泛范围内对其性能进行表征。我们将探讨低压极限，包括更完整地描述淬火所需的氮气分压。我们将开发技术来监测剩余的Rb，并隔离浓缩的Rb，延长使用寿命。我们将采用技术对纯缓冲气体进行再循环，最大限度地减少它们的消耗。我们将把这些技术组装成一个偏振器平台，具有更大的气体流动和冻结能力，以及一个更多功能和更高效的氙气输送系统。我们将优化一款能够以20 L/小时、50%偏振的速度生产Magnixene}的原型高流量偏振器，以满足临床合作伙伴和制药客户的需求。在第二阶段项目之后，偏光镜技术将完成，并为FDA批准为2类设备所需的详细工程和广泛的文件做好准备。

DESCRIPTION (provided by applicant): Hyperpolarized xenon-129 (HXe) MRI has been demonstrated to have exquisite sensitivity for functional diagnostic imaging of lungs, likely the most technically promising and commercially viable technique. Full characterization of pulmonary health may benefit from as many as eight different multi-liter protocols, which should ideally be completed in well under an hour. Three years ago our group identified an efficient method for polarization and developed an apparatus to exploit the high flow, low pressure polarization regime, increasing output by more than a factor of ten to 1 L/hr at 50%. In our Phase 1 proposal we argued that assembling a polarizer with several heat-conducting channels operating in parallel would permit a scale up by a factor of the number of channels, assuming similar conditions of temperature, pressure, laser illumination, and cell geometry. Furthermore, if the laser spectrum could be narrowed, then dropping the pressure by a factor of two could yield another two-fold improvement in production rate. During Phase 1 we developed new fabrication techniques, assembled a copper prototype, adapted our existing laser and magnetic infrastructure for its installation, and characterized its performance. We confirmed predictions, that the multi-channel polarizer column delivers HXe with >50% polarization at a rate of two liters per hour per hundred watts of narrowed laser power, up to 250 watts, a six-fold improvement over our previous world's best production rate. We discovered that birefringence arising from thermal stresses in a few laser elements was compromising polarization demonstrations of our copper-column technology up to the full kilowatt of available laser power, a problem that can now be easily corrected. In Phase 2 we propose full characterization of our new prototype polarizer, demonstrating twenty- fold scale up of xenon polarizer production output. We will characterize its performance over wide ranges of gas mixture, pressure, temperature, flow rates, and laser power. We will probe the low pressure limit, including a more complete characterization of the nitrogen partial pressure required for quenching. We will develop technology to monitor remaining rubidium and to sequester condensed rubidium, extending the service lifetime. We will incorporate technology to recirculate the pure buffer gases, minimizing their consumption. We will assemble these technologies into a polarizer platform with expanded gas flow and freeze-out capabilities, and a more versatile and efficient xenon delivery system. We will optimize a prototype high-flow polarizer capable of producing MagniXene} at 20 L/hr at 50% polarization, which meets the needs of clinical partners and pharmaceutical customers. After this Phase 2 project the polarizer technology will be completed, and ready for the detailed engineering and extensive documentation required for FDA approval as a Class 2 device.