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.

项目概要 在第二阶段 SBIR 应用中，我们将在第一阶段进展的基础上将 qF-ProbeTM 商业化 术中定量测量开颅脑期间 ALA 诱导的 PpIX 浓度 (CPpIX) 具体来说，在第一阶段，我们开发了一次性探针设计和原型。 其性能可与我们已建立的可重复使用的临床研究探针相媲美，并创建了一种仪器 符合临床用户规范的设计，保持与我们现有的高精度/重复性相当的准确性/重复性 qF-ProbeTM 具有适应其他荧光团的额外灵活性。 这一概念是作为 NIH 资助（R01 NS052274-09；PI：Roberts）荧光引导手术的一部分而出现的 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。 随后，该合作的高级成员创立了 Surgical Technologies LLC，他们带来了 丰富的领域专业知识特别及时，因为 (i) ALA-PpIX 荧光引导。 手术已获得 FDA 批准用于治疗高级别神经胶质瘤，(ii) 重大公司举措发生在 荧光引导手术表明了一个重要的全球市场（例如，Stryker 购买 NOVADAC 用于 2017 年约 7 亿美元，手术机器人市场领导者 Intuitive 纳入荧光检测 外科），(iii) 其他医疗科技公司（例如美敦力、蔡司）的兴趣很高，以及 (iv) 广泛 临床结果表明定量 CPpIX 相对于定性和主观视觉具有显着优势 事实上，我们的研究级仪器和可重复使用的探针已部署在 美国 2 个主要中心的超过 200 名脑肿瘤患者证明 PpIX 荧光水平不可见 或使用市售系统（例如 Zeiss Blue 400）可检测到的结果可以进行量化。 白光切除结束时检测残留肿瘤的灵敏度和特异性显着提高， 能够更彻底地切除肿瘤，包括低级别和高级别肿瘤，qF-。 ProbeTM 可以进行修改以检测 (i) 其他荧光团，(ii) 切除床以下深度和肿瘤内的肿瘤 血液薄膜的存在，以及（iii）同一病例中存在多个荧光团这些功能将是。 InSight 的业务计划将 qF-ProbeTM 定位为第一个推向市场的产品， 确定手术期间荧光团定量的临床价值 在第二阶段，我们将最终确定探针。 和仪器设计在全面的 QMS 设计控制下并符合行业法规，生产 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。