Scale Up of Hyperpolarized Xe Production

描述（由申请人提供）：超偏振氙-129 (HXe) MRI已被证明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，并开发了一种利用高流量，低压极化制度的设备，在50%的情况下将产量提高了十倍以上，达到1升/小时。在我们的第一阶段建议中，我们认为，在假设温度、压力、激光照明和电池几何形状相似的条件下，将一个具有多个并行运行的导热通道的偏振片组装在一起，可以使通道数量增加一倍。此外，如果激光光谱可以缩小，那么将压力降低两倍可以使生产率提高两倍。在第一阶段，我们开发了新的制造技术，组装了一个铜原型，改造了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，多通道偏振柱提供的HXe具有bbbb50 50%的偏振率，每100瓦的狭窄激光功率为每小时2升，最高可达250瓦，比我们之前世界上最好的生产速度提高了6倍。我们发现，在一些激光元件中，由于热应力引起的双折射影响了我们的铜柱技术的偏振演示，直至可用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，我们提出了我们的新原型偏振片的全面表征，展示了20倍的氙气偏振片生产产量。我们将描述其在各种气体混合物、压力、温度、流量和激光功率下的性能。我们将探讨低压极限，包括更完整地表征淬火所需的氮气分压。我们将开发监测剩余铷和隔离凝聚铷的技术，延长使用寿命。我们将采用技术对纯缓冲气体进行再循环，最大限度地减少其消耗。我们将把这些技术整合到一个具有扩大气体流量和冻结能力的偏光平台，以及一个更通用、更高效的氙气输送系统。我们将优化一个原型高流量偏振器，能够在50%偏振度下以20 L/hr的速度生产MagniXene}，以满足临床合作伙伴和制药客户的需求。在这个第二阶段项目之后，偏振器技术将完成，并准备好详细的工程和FDA批准的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.