Scale Up of Hyperpolarized Xe Production

描述（由申请人提供）：已证明超极化氙-129（HPLF）MRI对肺部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。肺部健康的全面表征可能受益于多达八种不同的多升方案，理想情况下，这些方案应在一小时内完成。三年前，我们的团队确定了一种有效的极化方法，并开发了一种设备，以利用高流量，低压极化制度，增加产量超过10到1升/小时的50%。在我们的第一阶段的建议，我们认为，组装一个偏振器与几个导热通道并行工作将允许放大的通道数量的一个因素，假设类似的条件下的温度，压力，激光照明，和细胞的几何形状。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一倍。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，并对其性能进行了表征。我们证实了预测，即多通道偏振器柱以每小时2升/百瓦的窄激光功率（高达250瓦）的速率提供具有>50%偏振的HPLF，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会损害我们的铜柱技术的偏振演示，直到可用激光功率达到整千瓦，这个问题现在可以很容易地纠正。在第二阶段，我们提出了我们的新的原型偏振器的全面表征，展示了二十倍的规模扩大氙气偏振器的生产输出。我们将在气体混合物、压力、温度、流速和激光功率的广泛范围内表征其性能。我们将探讨低压极限，包括淬火所需的氮气分压的更完整表征。我们将开发技术来监测剩余的铷和隔离浓缩的铷，延长使用寿命。我们将采用再循环纯缓冲气体的技术，最大限度地减少其消耗。我们将把这些技术组装成一个偏振器平台，它具有更大的气流和冻结能力，以及更通用和更有效的氙气输送系统。我们将优化原型高流量偏光器，能够以20 L/hr的速度在50%的偏光下生产MagniXene，满足临床合作伙伴和制药客户的需求。在第2阶段项目之后，偏振器技术将完成，并准备好详细的工程和FDA批准为2类设备所需的大量文件。

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.