Probe for Quantitative Fluorescence. Phase 2

项目总结 在此第二阶段SBIR应用中，我们将在第一阶段将QF-ProbeTM商业化的进展基础上再接再厉 开颅脑手术中丙氨酸诱导的PPIX浓度(CPPIX)定量测定 肿瘤切除。具体地说，在第一阶段，我们开发了一次性探测器设计和原型，这些原型是 在性能上可与我们已建立的可重复使用的临床研究探头相媲美，并创造了一种仪器 符合临床用户规格的设计，保持与我们现有的高精度/重复性相当的精度/重复性 性能研究单位，并具有额外的灵活性，以适应其他荧光团。QF-ProbeTM 概念作为NIH-Funding(R01 NS052274-09；PI：Roberts)的一部分出现在荧光引导手术中 达特茅斯和多伦多的生物医学工程/光学和神经外科研究团队。洞察力 外科技术有限责任公司随后由该合作的高级成员创建，他们带来了 丰富的领域专业知识。商业化特别及时，因为(I)Ala-PpIX荧光引导 FDA已批准手术治疗高级别胶质瘤，(Ii)公司在 荧光引导手术预示着巨大的全球市场(例如，Stryker收购NOVADAC 2017年约7亿美元，手术机器人市场领先者采用荧光检测，直观 外科手术)，(Iii)其他医疗技术公司(例如美敦力、蔡司)的兴趣很高，以及(Iv)广泛的 临床结果显示，定量CPPIX比定性和主观视觉更具优势 荧光成像。事实上，我们的研究级仪器和可重复使用的探测器已经部署在 美国两个主要中心的200名脑瘤患者，并证明PpIX荧光水平不可见 或可用市售系统(例如蔡司蓝400)检测。这样做会导致 在白光切除结束时检测残留肿瘤的敏感性和特异性显著提高， 能够更彻底地切除肿瘤，包括低级别和高级别肿瘤。此外，QF- ProbeTM可以被修改以检测(I)其他荧光团，(Ii)位于切除床以下和 血液薄膜的存在，以及(Iii)在同一情况下存在多个荧光团。这些能力将是 在未来的产品中实施。Insight的业务计划将QF-ProbeTM定位为上市的第一款产品， 确定手术中荧光团定量的临床价值。在第二阶段，我们将最终确定探测器 和仪器设计在全面的质量管理体系设计控制下，符合行业法规，生产 到5个功能齐全的QF-ProbeTM系统，通过临床可用性和调查数据验证最终设计， 并向FDA申请510k监管许可。

PROJECT SUMMARY In this Phase II SBIR application, we will build on progress in Phase I to commercialize qF-ProbeTM for quantitative intraoperative measurement of ALA-induced PpIX concentration (CPpIX) during open-cranial brain tumor resection. Specifically, in Phase I, we developed a disposable probe design and prototypes that are comparable in performance to our established reusable clinical-research probes, and created an instrument design that meets clinical-user specifications, maintains accuracy/repeatability equivalent to our existing high- performance research units and has additional flexibility for adaptation to other fluorophores. The qF-ProbeTM concept arose as part of NIH-funding (R01 NS052274-09; PI: Roberts) in fluorescence-guided surgery involving biomedical engineering/optics and neurosurgical research teams at Dartmouth and Toronto. InSight Surgical Technologies LLC was then founded by the senior members of this collaboration who bring substantial domain expertise. Commercialization is particularly timely, since (i) ALA-PpIX fluorescence-guided surgery has been FDA approved for high-grade glioma, (ii) substantial corporate moves have occurred in fluorescence-guided surgery indicating a significant global market (e.g., Stryker purchase of NOVADAC for ~$700M in 2017, and incorporation of fluorescence detection by market leader in surgical robotics, Intuitive Surgical.), (iii) interest from other MedTech companies (e.g., Medtronic, Zeiss) is high, and (iv) the extensive clinical results demonstrate compelling advantages of quantitative CPpIX over qualitative and subjective visual fluorescence imaging. Indeed, our research-grade instrument and reusable probes have been deployed in >200 brain tumor patients at 2 major US centers and demonstrate that levels of PpIX fluorescence not visible or detectable with commercially-available systems (e.g., Zeiss Blue 400) can be quantified. Doing so results in significantly greater sensitivity and specificity for detection of residual tumor at end of white-light resection, enabling more complete tumor removal, including in low-grade as well as high-grade tumors. Additionally, qF- ProbeTM can be modified to detect (i) other fluorophores, (ii) tumor at depth below the resection bed and in the presence of a thin film of blood, and (iii) multiple fluorophores in the same case. These capabilities will be implemented in future products. InSight’s business plan positions qF-ProbeTM as the first product to market, establishing the clinical value of fluorophore quantification during surgery. In Phase II, we will finalize the probe and instrument designs under full QMS design-control and in compliance with industry regulations, produce up to 5 fully functional qF-ProbeTM systems, validate the final design through clinical usability and survey data, and apply to FDA for 510k regulatory clearance.