Probe for Quantitative Fluorescence. Phase 2

定量荧光探针。

• 批准号: 10161873
• 负责人: DAVID W ROBERTS
• 金额: $ 108.09万
• 依托单位: INSIGHT SURGICAL TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10161873
• 关键词: Automobile Driving; Beds; Biomedical Engineering; Blood; Brain Neoplasms; Businesses; Cephalic; Clinical; Clinical Research; Collaborations; Data; Detection; Device or Instrument Development; Devices; Evaluation; Excision; FDA approved; Feedback; Film; Fluorescence; Funding; Future; Glioma; Industry; Intellectual Property; Intuition; Light; Measurement; Mediation; Medical; Medical Device; Medical Device Designs; Multi-site clinical study; Operative Surgical Procedures; Optics; Patients; Performance; Phase; Positioning Attribute; Production; Progress Reports; Regulation; Research; Residual Tumors; Rights; Risk; Robotics; Sensitivity and Specificity; Site; Small Business Innovation Research Grant; Software Design; Surgeon; Surveys; System; Technology; Testing; Thinness; Time; United States National Institutes of Health; Validation; Visual; Work; brain tumor resection; career; clinically relevant; commercialization; cost; data acquisition; design; ergonomics; flexibility; fluorescence imaging; fluorescence-guided surgery; fluorophore; improved; insight; instrument; interest; invention; member; neurosurgery; performance tests; prototype; tumor; usability

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.

项目摘要 在此II阶段SBIR应用程序中，我们将基于I阶段的进展，以商业化QF-Probetm 开放性大脑期间ALA诱导的PPIX浓度（CPPIX）的定量术中测量 肿瘤切除。具体而言，在第一阶段，我们开发了一次性探针设计和原型 与我们已建立的可重复使用的临床研究探针相当，并创建了一种工具 符合临床用户规格的设计，保持准确性/可重复性等效于我们现有的高 绩效研究单位，并具有适应其他荧光团的灵活性。 QF-Probetm 概念是NIH资助的一部分（R01 NS052274-09； PI：Roberts） 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团队。洞察力 然后，手术技术有限责任公司由这项合作的高级成员创立 实质领域的专业知识。商业化特别及时，因为（i）ALA-PPIX荧光引导 手术已被FDA批准用于高级神经胶质瘤，（ii）发生了实质性的公司迁移 荧光引导的手术表明全球大量市场（例如，斯特赖克（Stryker 2017年〜7亿美元，并通过外科机器人技术领导者纳入荧光检测 外科手术。 临床结果证明了定量CPPIX比定性和主观视觉的令人信服的优势 荧光成像。确实，我们的研究级工具和可重复使用的探针已被部署 >美国2个主要中心的200名脑肿瘤患者，并证明不可见的PPIX荧光水平 或可以用商业可用的系统（例如，蔡司蓝色400）检测到。这样做导致 在白光切除末尾检测残留肿瘤的敏感性和特异性明显更高， 能够清除更完整的肿瘤，包括低级和高级肿瘤。另外，QF- 可以修改探针以检测（i）其他荧光团，（ii）切除床的深度和深度的肿瘤 在同一情况下，存在薄膜的血液和（iii）多个荧光团。这些功能将是 在未来的产品中实施。 Insight的业务计划将QF-Probetm定位为首个市场产品， 在手术过程中确定荧光团定量的临床价值。在第二阶段，我们将最终确定探针 以及完整QMS设计控制和遵守行业法规的仪器设计 至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监管清除率。