An integrated microfluidic device for patient-derived micro-organospheres

用于患者来源的微有机球的集成微流体装置

• 批准号: 10828576
• 负责人: Daniel Aaron Nelson
• 金额: $ 39.97万
• 依托单位: XILIS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10828576
• 关键词: Adopted; Antineoplastic Agents; Architecture; Area; Biological; Biopsy; Cancer Biology; Cancer Center; Cancer Diagnostics; Cells; Chemoresistance; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Colorectal Cancer; Commercial grade; Complex; Computer software; Development; Devices; Disease; Disinfection; Disparate; Drug Screening; Electronics; Emulsions; Endocrine; Engineering; Environmental Risk Factor; Excision; Funding; Generations; Genetic; Goals; Growth; Heart; Institutional Review Boards; Lead; Malignant Neoplasms; Manuals; Measures; Medical Device; Membrane; Microfluidic Microchips; Microfluidics; Modality; Modeling; Monitor; Multiple Myeloma; Oils; Organoids; Outcome; Patients; Phase; Polymers; Population Heterogeneity; Procedures; Process; Publishing; Pump; Recovery; Reporting; Reproducibility; Resistance; Sampling; Series; Site; Small Business Innovation Research Grant; Standardization; System; Testing; Therapeutic; Tube; Universities; Validation; Xenograft procedure; assay development; cancer clinical trial; cancer therapy; clinical care; clinically actionable; cost; design; diagnostic assay; drug development; experience; improved; instrument; malignant breast neoplasm; matrigel; metastatic colorectal; minimal risk; multidisciplinary; novel; operation; patient response; personalized medicine; polymerization; precision medicine; precision oncology; prototype; stem cells; success; treatment response

PROJECT SUMMARY/ABSTRACT Functional precision oncology holds great potential to improve the current clinical paradigm by using patient- derived ex vivo systems (e.g., PDXs and organoids) for personalized treatment-specific readouts. However, presently, these models take long to establish, are not scalable and are costly; such challenges impede their wide-spread applicability and commercial potential. Therefore, there remains an unmet need to develop novel functional precision medicine strategies that pair the right therapy to each patient to improve clinical outcomes. Xilis is answering this call by developing a novel FDA, CLIA and IVDR-compliant medical device that can rapidly grow micro-organospheres (MOS) – high-fidelity, ex vivo patient avatars. Xilis has developed a proprietary benchtop MOS generator instrument (MOSgen) to generate MOS based on the following processes: 1) formation of Matrigel droplet-based MOS “micro-reactors” in oil emulsions from low volume clinical samples (e.g., 18G biopsies) 2) polymerization of the Matrigel via heat through our unique chip design, 3) sample demulsification using our proprietary process, where the oil is removed, and the droplets are resuspended in media for downstream establishment. Although functional, the current MOSgen prototype has disparate, stand- alone workflows for MOS formation, polymerization and demulsification that need complex tubing, complicated user interaction, and requires lengthy disinfection procedures, which impedes its use and applicability in clinical workflows. Thus, in this SBIR Fast-track, our multi-disciplinary team with engineering, biological and clinical expertise will build an automated, end-to-end, commercial-grade MOSgen instrument that rapidly generates MOS in a scalable and reproducible manner with minimal risk of contamination. Xilis currently is engaged with its strategic partner, MD Anderson Cancer Center, and will implement the MOSgen into the existing clinical workflow to validate its operation. SBIR funding would also bolster Xilis’ collaboration with Mayo Clinic to enable device validation by supporting the NCI-funded BEAUTY clinical trials. In Phase I, we will develop a penultimate prototype of our MOSgen instrument, which will integrate the hardware and software workflows. We have engineered a series of novel serpentine microfluidic chipsets, which we will integrate into our instrument for an all-in-one solution. We will test the prototype using colorectal cancer samples (leveraging our registered clinical trial with leading site, MD Anderson) and multiple myeloma samples (from our collaboration with Duke University). In Phase II, we will build our end-to-end, commercial-grade MOSgen, in compliance with FDA’s QSR Part 320. This instrument will be automated and easy-to-use, to readily support seamless implementation into current clinical workflows. To test the MOSgen, we will partner will MD Anderson and Mayo Clinic (subaward) and integrate our instrument into existing clinical trials to validate its operation. Successful completion will support the development of a commercial, fully-automated, commercial-grade microfluidic instrument that can streamline the generation of MOS to enable robust functional precision medicine capabilities.

项目总结/摘要 功能精确肿瘤学具有很大的潜力，可以通过使用患者- 衍生的离体系统（例如，PDX和类器官），用于个性化治疗特异性读数。然而，在这方面， 目前，这些模型需要很长时间才能建立起来，不可扩展且成本高昂;这些挑战阻碍了它们的发展。 广泛的适用性和商业潜力。因此，仍然存在开发新颖的 功能性精准医疗策略，为每位患者提供正确的治疗，以改善临床结果。 Xilis正在响应这一呼吁，开发一种符合FDA、CLIA和IVDR标准的新型医疗器械， 生长微有机球体（MOS）-高保真，离体患者化身。Xilis开发了一种专有的 台式MOS发生器仪器（MOSgen），用于基于以下过程生成MOS：1） 在来自低体积临床样品的油乳液中形成基于基质胶液滴的MOS "微反应器"（例如， 18G活检）2）通过我们独特的芯片设计，通过加热使基质胶聚合，3）样品 使用我们的专有工艺进行破乳，其中油被去除，液滴重新悬浮在 下游建立的媒体。虽然功能，目前的MOSgen原型有不同的，立场- 用于MOS形成、聚合和破乳的单独工作流程，需要复杂的管道， 用户交互，并且需要冗长的消毒程序，这阻碍了其在临床中的使用和适用性 工作流程。因此，在这个SBIR快速通道中，我们的多学科团队，包括工程，生物和 临床专业知识将建立一个自动化，端到端，商业级MOSgen仪器， 以可扩展和可再现的方式产生MOS，污染风险最小。目前， 正在与其战略合作伙伴MD安德森癌症中心合作，并将在 现有的临床工作流程，以验证其操作。SBIR的资金还将加强Xilis与马约的合作 诊所通过支持NCI资助的BEAUTY临床试验来实现器械验证。在第一阶段，我们将开发 我们的MOSgen仪器的倒数第二个原型，它将集成硬件和软件工作流程。 我们已经设计了一系列新颖的蛇形微流控芯片组，我们将把它们集成到我们的仪器中。 实现一体化解决方案。我们将使用结直肠癌样本测试原型（利用我们注册的 临床试验，主要研究中心，MD安德森）和多发性骨髓瘤样本（来自我们与杜克的合作 大学）。在第二阶段，我们将建立我们的端到端，商业级MOSgen，符合FDA的QSR 第320部分。这一工具将是自动化的，易于使用，随时支持无缝实施， 当前临床工作流程。为了测试MOSgen，我们将与医学博士安德森和马约诊所（子合同）合作 并将我们的仪器整合到现有的临床试验中，以验证其操作。成功完成将支持 开发一种商业化的、全自动的、商业级的微流体仪器， MOS的产生，以实现强大的功能性精准医疗能力。