ADDITIVE MANUFACTURING OF PDMS MICROFLUIDICS

PDMS 微流控的增材制造

• 批准号: 10698810
• 负责人: Jeffery Schultz
• 金额: $ 106.66万
• 依托单位: PHASE, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-19 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698810
• 关键词: 3-Dimensional; 3D Print; Adopted; Adoption; Age; Animal Model; Architecture; Basement membrane; Biological; Biomanufacturing; Biotechnology; Blood - brain barrier anatomy; Cardiovascular Diseases; Cell Survival; Characteristics; Clinical Trials; Coculture Techniques; Collaborations; Communities; Development; Devices; Disease; Electrical Resistance; Electrodes; Endothelium; Ensure; Face; Familiarity; Formulation; Freedom; Growth; Hour; Human; In Vitro; Injections; Kinetics; Lasers; Legal patent; Light; Marketing; Measurement; Mechanics; Medicine; Membrane; Methods; Microfluidic Microchips; Microfluidics; Modeling; Molds; Patients; Performance; Permeability; Pharmacologic Substance; Phase; Play; Polymers; Porosity; Printing; Process; Production; Reproducibility; Research; Research Personnel; Resolution; Rheology; Risk; Role; Sampling; Source; System; Technology; Testing; Thick; Tight Junctions; Time; Toxic effect; Tube; Virginia; biological systems; commercialization; design; digital; drug discovery; drug testing; fabrication; human model; improved; in vitro Model; in vivo; innovation; kinetic model; knowledgebase; lithography; manufacture; manufacturing process; manufacturing technology; meter; models and simulation; nanofiber; nanomembrane; novel therapeutics; organ on a chip; particle; point-of-care diagnostics; polydimethylsiloxane; research and development; tool; 3-Dimensional; 3D Print; Adopted; Adoption; Age; Animal Model; Architecture; Basement membrane; Biological; Biomanufacturing; Biotechnology; Blood - brain barrier anatomy; Cardiovascular Diseases; Cell Survival; Characteristics; Clinical Trials; Coculture Techniques; Collaborations; Communities; Development; Devices; Disease; Electrical Resistance; Electrodes; Endothelium; Ensure; Face; Familiarity; Formulation; Freedom; Growth; Hour; Human; In Vitro; Injections; Kinetics; Lasers; Legal patent; Light; Marketing; Measurement; Mechanics; Medicine; Membrane; Methods; Microfluidic Microchips; Microfluidics; Modeling; Molds; Patients; Performance; Permeability; Pharmacologic Substance; Phase; Play; Polymers; Porosity; Printing; Process; Production; Reproducibility; Research; Research Personnel; Resolution; Rheology; Risk; Role; Sampling; Source; System; Technology; Testing; Thick; Tight Junctions; Time; Toxic effect; Tube; Virginia; biological systems; commercialization; design; digital; drug discovery; drug testing; fabrication; human model; improved; in vitro Model; in vivo; innovation; kinetic model; knowledgebase; lithography; manufacture; manufacturing process; manufacturing technology; meter; models and simulation; nanofiber; nanomembrane; novel therapeutics; organ on a chip; particle; point-of-care diagnostics; polydimethylsiloxane; research and development; tool

Development of new therapeutics often fails in human clinical trials due to the biological differences between humans and animal models and the inability of current in vitro models to accurately recapitulate the in vivo state. As such, in vitro microfluidic (MF) models have seen significant growth and become a key tool for understanding biological systems, and for testing and development of new therapeutics. Innovation in microfluidics, however, is limited by materials and manufacturing challenges associated with conventional processes such as soft lithography, injection molding, and mechanical milling. Additive manufacturing (AM), also referred to as 3D printing, has been heralded as the solution to these manufacturing challenges and AM additionally offers broad design freedom not accessible via conventional manufacturing. However, AM faces a critical hurdle: the limited ability to 3D print conventional (thermally-curable) polydimethylsiloxane (PDMS), the most widely established R&D microfluidic material. Despite the potential manufacturing and design benefits, AM has not been broadly adopted for MF production due in large part to the potential material risks. Of the commercially available AM processes and those being researched, none offer a clear path to commercial 3D printing of conventional PDMS MF devices. Our hypothesis is: combining the knowledge-base and familiarity of conventional PDMS with our 3D PDMS process will fundamentally change the way microfluidics are fabricated and unlock the design freedom of additive manufacturing for the MF community, which will lead to significant advancements of in vitro MF models. Building upon our successful Phase I effort — during which we demonstrated the ability of our patent-pending 3D PDMS process to 3D print MF devices from conventional PDMS — this Phase II effort focuses on developing a pilot-scale commercial 3D PDMS system and using the 3D PDMS process to fabricate cutting edge in vitro blood-brain-barrier models for testing by our collaborators at Virginia Tech. They recently developed a MF BBB model containing a nanofiber basement membrane mimic which demonstrates a superior ability to recapitulate the in vivo BBB architecture. In Phase II, the team will optimize the architecture of the nanomembranes and then design and demonstrate a commercially producible 3D PDMS MF nanomembrane BBB model with integrated electrodes. We will also collaborate with the Nadkarni group at Harvard MGH to characterize the PDMS curing kinetics in 3D PDMS printing using laser speckle rheology. Aim 1: Operational Pilot-Scale 3D PDMS System. The objective of this aim is to design and a build pilot-scale 3D PDMS system. Milestone 1A: 3D PDMS Simulation & Model Accurately Predict Curing within +/-10%; Milestone 1A: 3D PDMS Simulation Model Accurately Predicts Curing within +/-10%; Milestone 1B: 3D PDMS unit achieves 200 mm3/hr build rate for MF device. Aim 2: 3D Printed Nanofiber Blood-Brain-Barrier Model. The objective of this aim is to 3D print a highly reproducible BBB model which incorporates a nanofiber membrane and integrated TEER electrodes. Milestone 2A: Transport master curves for nanofiber membranes developed; Milestone 2B: Optimized nanofiber BBB model demonstrated by a 20% increase in TEER values for a co- culture sample as compared to a monoculture sample. Project Summary/Abstract

由于人类和 动物模型和当前体外模型无法准确概括体内状态。因此，体外微流体（MF） 模型已经看到了显着的增长，并成为理解生物系统的关键工具，并用于测试和开发 新理论。但是 传统的过程，例如软岩性摄影，注射成型和机械铣削。增材制造（AM），也推荐 对于3D打印，已被预示为解决这些制造挑战的解决方案，AM还提供广泛的设计 自由无法通过常规制造访问。但是，AM面临着一个关键的障碍：3D打印常规的能力有限 （可热疗法）聚二甲基硅氧烷（PDMS），这是最广泛建立的R＆D微流体材料。尽管有潜力 制造和设计优势，AM在很大程度上归因于潜在的材料风险很大程度上并未广泛用于MF生产。 在商业上可用的AM流程和正在研究的过程中，没有一个为商业3D打印的清晰途径 常规的PDMS MF设备。我们的假设是：将常规PDM的知识基础和熟悉与我们的3D结合在一起 PDMS流程将从根本上改变微流体制造的方式，并解锁添加剂制造的设计自由 对于MF社区，这将导致体外MF模型的重大进步。 在我们成功的I阶段努力的基础上 - 在此期间，我们证明了我们的专利申请3D PDMS流程的能力 从传统PDM到3D打印MF设备 - 这二阶段的工作重点是开发飞行员大型商业3D PDMS系统 并使用3D PDMS工艺在弗吉尼亚州的合作者进行测试来制造体外血脑屏障模型的尖端 技术。他们最近开发了一个MF BBB模型，该模型包含一个纳米纤维基底膜模拟物，该模拟显示出优质 概括体内BBB体系结构的能力。在第二阶段，团队将优化纳米膜的体系结构，然后 设计并展示了具有集成电极的商业生产的3D PDMS MF纳米膜BBB模型。我们也会 与Harvard MGH的Nadkarni集团合作，以使用激光Specle在3D PDMS印刷中的PDMS固化动力学表征 流变学。 AIM 1：操作试验尺度3D PDMS系统。此目的的目的是设计和建立飞行员尺度的3D PDM 系统。里程碑1A：3D PDMS模拟和模型准确预测+/- 10％内的固化；里程碑1A：3D PDMS模拟 模型准确预测+/- 10％内的固化； Milestone 1B：3D PDMS单位可实现MF设备的200 mm3/hr构建率。 AIM 2：3D打印的纳米纤维血脑屏障模型。此目的的目的是打印高度可再现的BBB 结合纳米纤维膜和集成的TEER电极的模型。里程碑2A：纳米纤维的运输主曲线 膜开发；里程碑2B：优化的纳米纤维BBB模型，通过共同值增加了20％ 与单一文化样本相比，培养样品。 项目摘要/摘要