An integrated microfluidic device for patient-derived micro-organospheres

项目摘要/摘要 功能精确肿瘤学具有巨大的潜力，可以通过使用患者- 衍生的体外系统(例如，PDX和有机化合物)，用于个性化的治疗特定读数。然而， 目前，这些模式需要很长时间才能建立，而且不可扩展，而且成本高昂；这些挑战阻碍了它们的发展 具有广泛的适用性和商业潜力。因此，开发小说的需求仍然没有得到满足。 功能精准医学策略，为每个患者配对正确的治疗方法，以改善临床结果。 Xilis正在通过开发一种符合FDA、CLIA和IVDR的新型医疗设备来响应这一呼吁，该设备可以快速 培养微型有机球体(MOS)-高保真、体外患者化身。Xilis开发了一种专有的 台式MOS生成器(MOSgen)基于以下流程生成MOS：1) 在来自低容量临床样本的油乳剂中形成基于Matrigel液滴的MOS“微反应器”(例如， 18G活组织检查)2)通过我们独特的芯片设计加热聚合Matrigel，3)样品 使用我们专有的过程进行破乳，将油去除，液滴重新悬浮在 用于下游建立的媒体。虽然功能强大，但目前的MOSgen原型具有完全不同的、标准的- MOS的形成、聚合和破乳的单独工作流程需要复杂的管道、复杂的 用户交互，需要冗长的消毒程序，这阻碍了其在临床上的使用和适用性 工作流程。因此，在SBIR快速通道中，我们的多学科团队拥有工程、生物和 临床专家将构建一种自动化的、端到端的商业级MOSgen仪器， 以可扩展和可重复的方式生成MOS，并将污染风险降至最低。Xilis目前 正在与其战略合作伙伴MD Anderson癌症中心合作，并将把MOSgen实施到 现有的临床工作流程，以验证其操作。SBIR的资金也将加强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型的蛇形微流控芯片组，我们将把它们集成到我们的仪器中 提供一体式解决方案。我们将使用结直肠癌样本测试原型(利用我们注册的 领先站点的临床试验，MD Anderson)和多发性骨髓瘤样本(来自我们与Duke的合作 大学)。在第二阶段，我们将按照FDA的QSR建立我们的端到端、商业级MOSgen 第320部分。该仪器将自动化且易于使用，可随时支持无缝实施 当前的临床工作流程。为了测试MOSgen，我们将与威尔·MD·安德森和梅奥诊所(分奖)合作 并将我们的仪器集成到现有的临床试验中，以验证其操作。成功完成将支持 开发一种商用、全自动化、商业级的微流控仪器，可以简化 MOS的生成使功能强大的精准医疗功能得以实现。

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.