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.

项目摘要/摘要 功能精度肿瘤学具有巨大的潜力，可以通过使用患者 - 用于个性化治疗的读数的派生的离体系统（例如PDX和类器官）。然而， 目前，这些模型需要很长时间才能扩展，而且代价高昂。这样的挑战阻碍了他们的 广泛的适用性和商业潜力。因此，尚未满足发展小说的需求 功能精确的医学策略，将正确的疗法与每个患者配对以改善临床结果。 Xilis正在通过开发一种新颖的FDA，CLIA和IVDR兼容的医疗设备来接听这个电话，该设备可以迅速 生长的微孔圈（MOS） - 高保真性，离体患者化身。 Xilis已经开发了专有 台式MOS发电机仪器（MOSGEN）基于以下过程生成MOS：1） 来自低体积临床样品的油乳液中基于Matrigel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热量将矩阵聚合的聚合，3）样品 使用我们的专有工艺进行拆除，去除油，然后将液滴恢复 下游建立的媒体。尽管功能很强，但当前的Mosgen原型具有不同的，独立的 单独的工作流程，用于MOS组成，聚合和拆除需要复杂的管道，复杂的工作流程 用户互动，需要长时间的消毒程序，这阻碍了其在临床上的使用和适用性 工作流程。在这个SBIR快速轨道中，我们的多学科团队具有工程，生物学和 临床专业知识将建立一种自动，端到端的商业级Mosgen仪器，迅速 以可扩展且可再现的方式生成MOS，污染风险最小。 Xilis目前 与其战略合作伙伴MD Anderson癌症中心互动，并将将MOSGEN实施到 现有的临床工作流程以验证其操作。 SBIR资金还将加强Xilis与Mayo的合作 诊所通过支持NCI资助的美容临床试验来实现设备验证。在第一阶段，我们将发展 MOSGEN仪器的倒数第二个原型，它将整合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体芯片组，我们将将其集成到我们的仪器中 用于多合一解决方案。我们将使用结直肠癌样品测试原型（利用我们的注册 与领先地点MD Anderson的临床试验）和多个骨髓瘤样品（来自我们与Duke的合作 大学）。在第二阶段，我们将按照FDA的QSR构建我们的端到端商业级Mosgen 第320部分。此仪器将是自动化且易于使用的，可以轻松地支持无缝实现 当前的临床工作流程。为了测试MOSGEN，我们将合作MD Anderson和Mayo Clinic（Subaward） 并将我们的仪器集成到现有的临床试验中，以验证其运作。成功完成将支持 可以简化的商业，全自动，商业级的微流体仪器的开发 MOS的产生可实现强大的功能精确药物功能。