ADDITIVE MANUFACTURING OF PDMS MICROFLUIDICS

PDMS 微流控的增材制造

基本信息

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
项目类别：
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

项目摘要

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

由于人类和人类之间的生物学差异，新疗法的开发经常在人体临床试验中失败。动物模型以及当前体外模型无法准确重现体内状态，因此，体外微流体（MF）。模型已经取得了显着的增长，并成为理解生物系统以及测试和开发生物系统的关键工具。然而，微流体技术的创新受到与相关材料和制造挑战的限制。传统工艺，如软光刻、注塑和机械铣削，也称为增材制造 (AM)。 3D 打印被认为是这些制造挑战的解决方案，而增材制造还提供了广泛的设计然而，增材制造面临着一个关键障碍：传统 3D 打印的能力有限。（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，尽管具有潜力。制造和设计方面的优势，增材制造尚未广泛应用于增材制造生产，很大程度上是由于潜在的材料风险。在商业化的增材制造工艺和正在研究的工艺中，没有一个能够提供商业 3D 打印的明确途径。我们的假设是：将传统 PDMS 的知识库和熟悉程度与我们的 3D 相结合。 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对于 MF 界来说，这将导致体外 MF 模型的重大进步。以我们成功的第一阶段努力为基础，在此期间我们展示了正在申请专利的 3D PDMS 工艺的能力从传统 PDMS 到 3D 打印 MF 设备——第二阶段工作重点是开发中试规模的商业 3D PDMS 系统并使用 3D PDMS 工艺制造尖端的体外血脑屏障模型，供我们在弗吉尼亚州的合作者进行测试他们最近开发了一种包含纳米纤维基底膜模拟物的 MF BBB 模型，该模型表现出优越的性能。在第二阶段，该团队将优化纳米膜的结构，然后重新构建体内 BBB 结构。我们还将设计并演示可商业化生产的带有集成电极的 3D PDMS MF 纳米膜 BBB 模型。与哈佛大学 MGH 的 Nadkarni 小组合作，利用激光散斑表征 3D PDMS 打印中的 PDMS 固化动力学流变学。目标 1：可操作的中试规模 3D PDMS 系统该目标的目标是设计和构建中试规模 3D PDMS。里程碑 1A：3D PDMS 模拟和模型在 +/-10% 范围内准确预测固化里程碑 1A：3D PDMS 模拟；模型准确预测固化在 +/-10% 范围内；里程碑 1B：3D PDMS 单元实现 MF 设备的 200 mm3/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标是 3D 打印高度可重复的 BBB。模型包含纳米纤维膜和集成 TEER 电极：里程碑 2A：纳米纤维的传输主曲线。开发出膜；里程碑 2B：优化的纳米纤维 BBB 模型，其 TEER 值增加了 20% 培养样品与单一培养样品相比。项目概要/摘要