TR&D-4: Growing Tissue in the Scalable, Modular, Automated, and Closed (SMAC) Foundry

项目概要/摘要： TR&D-4将在ARMI上演示过程自动化|BioFabUSA的Tissue Foundry是一个可扩展的模块化， 自动化和封闭的组织制造平台。组织铸造厂是一个集成的主要场外- 架子组件来执行生产纸巾的顺序的模块化步骤。组织铸造自动化 解冻一小瓶贴壁细胞，在搅拌罐容器中的微载体上扩增它们，收获细胞， 将细胞交换到促进后续分化或组织发育步骤的培养基中， 组织在成熟过程中，以及最终产品的保存和包装。重新设计手工流程 到封闭的，自动化的组织铸造过程，ARMI的深层组织表征中心解构了一个 手动处理并在终点和中间阶段开发组织类型特定的设定点 在细胞的深度多参数表征之后使用实验和建模进行生产， 组织.一旦确定了这些设定点，可用的组织特定传感器中仍存在显著差距， 用于控制和监测组织质量的设备。 先进的传感器技术（在TR&D-1和-2中开发）和原型，启用执行器 生物反应器（TR&D-3）将被集成到组织铸造厂，并通过生产证明 组织制造相关环境中的CP靶组织。这一目标将在3年内实现 具体目标：目标1：传感器与Tissue Foundry细胞培养系统的物理集成。我们将 将在TR&D-1、-2和-3中开发的新开发的生物传感器集成到组织铸造中， 测量组织过程的特定参数，并作为可行性的概念证明， 通过反馈回路控制这些过程。目标2：通过集成传感器和 Tissue Foundry骨干自动化和数据管理系统。组织铸造 控制基于监控和数据采集（SCADA）架构，并使用 可编程逻辑控制器（PLC），它将直接与传感器和执行器接口， 处理步骤和实时反馈控制。目标3：自动化生产多达10种组织 同步从CCMEEC的关节软骨开始， 评估以确定最佳的自动化和传感器实施。一旦配置完成，组织铸造厂将 可用于使用集成生物指导生物反应器同时生产多达10个组织。数据从每个 步骤和最终产品将通过集成传感器收集，分析培养基等分试样，并进行破坏性分析。 取样以比较手动和自动化过程。TR&D4将提供自动化制造 系统，利用原型组织铸造厂的现有模块， TR&D-1、-2和-3开发的可靠生产复杂组织的能力

Project Summary/Abstract: TR&D-4 will demonstrate process automation on ARMI|BioFabUSA’s Tissue Foundry, a scalable, modular, automated and closed tissue manufacturing platform. The Tissue Foundry is the integration of primarily off-the- shelf components to perform the sequential, modular steps of producing a tissue. The Tissue Foundry automates thawing a vial of adherent cells, expanding them on microcarriers in stirred tank vessels, harvesting cells and exchanging cells into media promoting subsequent differentiation or tissue development steps, culturing the tissues during maturation, and preservation and packaging of the final product. To re-design the manual process to the closed, automated Tissue Foundry process, ARMI’s Deep Tissue Characterization Center deconstructs a manual process and develops tissue-type specific setpoints at both the endpoint and at intermediate stages of production using experimentation and modeling after deep multiparameter characterization of the cells and tissue. Once these setpoints are identified significant gaps remain in available tissue specific sensors and equipment to control and monitor tissue quality. Advanced sensor technologies (developed in TR&D-1 and –2) and prototype, actuator-enabled bioreactors (TR&D-3) will be integrated into the Tissue Foundry and demonstrated through production of CP target tissues in a tissue manufacturing relevant environment. This objective will be carried out in 3 specific aims: Aim 1: Physical integration of sensors with Tissue Foundry cell culture system. We will integrate newly-developed biosensors developed in TR&D-1, -2, and -3 into the Tissue Foundry for both measurement of parameters specific to the tissue process, and as a proof of concept for the feasibility of controlling these processes through feedback loops. Aim 2: Efficient control by integration of sensors and actuators with Tissue Foundry backbone automation and data management system. Tissue Foundry control is based on a supervisory control and data acquisition (SCADA) architecture and on the use of programmable logic controllers (PLCs), which will interface directly with sensors and actuators executing processing steps and real-time feedback control. Aim 3: Automated production of up to 10 tissues simultaneously. A manual tissue engineering process, starting with CCMEEC’s articular cartilage, will be assessed to identify optimal automation and sensor implementation. Once configured, the Tissue Foundry will be used to produce up to 10 tissues simultaneously using integrated bio-instructive bioreactors. Data from each step and the final product will be collected through integrated sensors, analysis of media aliquots, and destructive sampling to compare the manual and automated processes. TR&D4 will deliver an automated manufacturing system, leveraging the existing modules of the prototype Tissue Foundry, with vastly improved capabilities developed by TR&D-1, -2, and -3, for reliably producing complex tissues