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

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

由于人与人之间的生物学差异，新疗法的开发在人类临床试验中经常失败， 动物模型和目前的体外模型不能准确地再现体内状态。因此，体外微流体（MF） 模型已经有了显著的增长，并成为理解生物系统的关键工具， 新疗法然而，微流体技术的创新受到材料和制造挑战的限制， 常规工艺，例如软光刻、注射成型和机械研磨。增材制造（AM），也称为 作为3D打印，已被誉为这些制造挑战的解决方案，AM还提供广泛的设计 传统制造业无法获得的自由。然而，AM面临着一个关键的障碍：3D打印传统的能力有限， （可热固化）聚二甲基硅氧烷（PDMS）是最广泛建立的研发微流体材料。尽管潜在的 尽管增材制造在制造和设计方面具有优势，但由于潜在的材料风险，增材制造尚未被广泛用于MF生产。 在商业上可用的AM工艺和正在研究的AM工艺中，没有一个提供了商业3D打印的明确途径。 常规PDMS MF装置。我们的假设是：将传统PDMS的知识基础和熟悉程度与我们的3D PDMS工艺将从根本上改变微流体的制造方式，并释放增材制造的设计自由度 为MF社区，这将导致显着的进步，在体外MF模型。 在我们成功的第一阶段工作的基础上，我们展示了正在申请专利的3D PDMS工艺的能力。 从传统的PDMS 3D打印MF设备-这第二阶段的工作重点是开发一个试点规模的商业3D PDMS系统 并使用3D PDMS工艺制造尖端的体外血脑屏障模型，供我们在弗吉尼亚的合作者进行测试 Tech.他们最近开发了一种MF BBB模型，该模型含有一种基底膜模拟物上级 重现体内BBB结构的能力。在第二阶段，研究小组将优化纳米膜的结构， 设计并展示了一个商业化生产的3D PDMS MF纳米膜BBB模型与集成电极。我们还将 与哈佛MGH的Nadkarni小组合作，使用激光散斑表征3D PDMS打印中的PDMS固化动力学 流变学 目标1：操作中试规模的3D PDMS系统。本研究的目的是设计和建立中试规模的三维PDMS 系统里程碑1A：3D PDMS模拟和模型准确预测固化在+/-10%以内;里程碑1A：3D PDMS模拟 模型准确预测固化在+/-10%范围内;里程碑1B：3D PDMS装置实现MF器械的200 mm 3/hr构建速率。 目标2：3D打印纳米纤维血脑屏障模型。该目标的目的是3D打印高度可再现的BBB。 该模型结合了一个隔膜和集成TEER电极。里程碑2A：运输主曲线 里程碑2B：优化的BABBBB模型，通过共聚合物的TEER值增加20%来证明。 培养物样品与单一培养物样品相比。 项目总结/摘要