Probe for Quantitative Fluorescence. Phase 2

项目摘要 在第二阶段SBIR应用中，我们将在第一阶段的基础上，将qF-ProbeTM商业化， 开颅手术中ALA诱导的PpIX浓度（CPpIX）的术中定量测量 肿瘤切除术具体来说，在第一阶段，我们开发了一次性探头设计和原型， 与我们建立的可重复使用的临床研究探针的性能相当，并创造了一种仪器 符合临床用户规范的设计，保持与我们现有的高精度/可重复性相当的精度/可重复性， 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 这一概念作为荧光引导手术NIH资助（R 01 NS 052274 -09; PI：Roberts）的一部分而出现 涉及达特茅斯和多伦多的生物医学工程/光学和神经外科研究小组。洞察力 Surgical Technologies LLC随后由该合作的高级成员创立， 丰富的专业知识。商业化是特别及时的，因为（i）ALA-PpIX荧光引导的 手术已被FDA批准用于高级别胶质瘤，（ii）大量的公司行动已经发生在 荧光引导的手术表明了重要的全球市场（例如，斯特赖克购买NOVADAC， 2017年约7亿美元，并纳入手术机器人市场领导者Intuitive的荧光检测 外科手术），(iii)其他医疗技术公司的兴趣（例如，美敦力，蔡司）是高，和（四）广泛的 临床结果证明定量CPpIX相对于定性和主观目视检查的显著优势 荧光成像事实上，我们的研究级仪器和可重复使用的探针已经部署在 >200例脑肿瘤患者在2个主要的美国中心，并证明PpIX荧光水平不可见 或者可以用市售系统检测（例如，Zeiss Blue 400）。这样做导致 在白光切除术结束时检测残留肿瘤的灵敏度和特异性显著更高， 能够更完全地切除肿瘤，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）在切除床下方的深度处和在切除床中的肿瘤。 血液薄膜的存在，和（iii）在同一情况下的多个荧光团。这些能力 在未来的产品中实现。InSight的商业计划将qF-ProbeTM定位为第一个推向市场的产品， 建立了手术期间荧光团定量的临床价值。在第二阶段，我们将完成探测 在全面的QMS设计控制和符合行业法规的情况下， 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510 k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.