ADDITIVE MANUFACTURING OF PDMS MICROFLUIDICS

PDMS 微流控的增材制造

基本信息

批准号：
10324424
负责人：
Jeffery Schultz
金额：
$ 17.36万
依托单位：
PHASE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2022-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10324424
关键词：
3-Dimensional 3D Print Address Advanced Development Biological Blood - brain barrier anatomy Cells Characteristics Clinical Clinical Trials Complex Cultured Cells Device or Instrument Development Devices Disease Electrical Resistance Electrodes Elements Environment Face Foundations Future Hour Human In Vitro Laboratory Research Legal patent Liquid substance Malignant neoplasm of brain Measurement Measures Medical Medicine Membrane Microfluidic Microchips Microfluidics Modality Modeling Needles Optics Patients Performance Permeability Pharmacologic Substance Phase Phenotype Physiological Polyesters Polymers Process Proteins Quick Test for Liver Function Research Personnel Resolution Shapes Small Business Innovation Research Grant Structure Technology Testing Tight Junctions Time Transport Process base blood-brain barrier disruption brain endothelial cell commercialization design drug testing effective therapy elastomeric electric field fluorescein isothiocyanate dextran in vivo monolayer organ on a chip pressure shear stress simulation success

项目摘要

Properly simulating an in vivo biological environment in vitro generally leads to increased clinical trial success and more rapid access to effective treatments. Microfluidics are a primary means of simulating biological environments in clinical and pharmaceutical laboratory research; however, the current utility of microfluidics is limited by materials and manufacturing challenges. Additive manufacturing (3D printing) has been heralded as the solution to these challenges, but it also faces hurdles, such as a relatively large minimum feature size and difficulty in removing excess build material from internal passages. Additive manufacturing has the potential to build complex, 3D, bio-mimicking structures and solve key challenges in microfluidics such as fabricating efficient mixing elements, incorporating of membranes or electrodes, providing integrated valving, and simplifying the connection between the micro-and macro-scales. However, the most promising and widely used material in microfluidics, PDMS, is currently not available for additive manufacturing. Phase, Inc. has developed a proprietary additive manufacturing technology termed electric field fabrication (EFF) based on liquid dielectrophoresis that shapes uncured PDMS into prescribed cross-sections which can be cured and bonded in succession to build a 3D microfluidic device. As opposed to other 3DP modalities, our patented approach offers unique control over the 3D printing process, opening the door to print new materials such as elastomerics with unprecedented resolution and no post- processing. This technology offers the potential to increase the design space of PDMS microfluidics to more closely match the in vivo environment enabling future advances in technologies such as organ-on-a- chip. Commercialization of an additive manufacturing platform for complex 3D PDMS microfluidic devices will enable broad access to 3D bio-mimicking structures which result in more effective treatments. The microfluidics market is now valued at $14 billion and is expected to grow to $31 billion by 2027. PDMS based products make up approximately 30% of the microfluidics market—the largest share of the market. The proposed Phase I effort will further enhance the fidelity of the EFF process for additively manufacturing PDMS devices through refinement of the overall platform and specifically address two aims which are foundational to the commercial viability of the process. The Phase I effort will 1) demonstrate the functional performance of a representative device and 2) demonstrate the ability to successfully incorporate a membrane into a microfluidic device. The aims of this Phase 1 SBIR proposal are to: Aim 1. Fabricate a representative 3D microfluidic device in PDMS. To demonstrate the broad ranging utility of the EFF process, a representative microfluid device will be fabricated in PDMS with two inlets, a passive mixing element, an observation/measurement channel and an outlet. Successful demonstration of additively manufacturing these basic microfluidic building blocks in a PDMS device will be the launching point for fabrication of specific devices for trial studies and further commercialization. Aim 2. Fabricate a PDMS device with an integrated track-etched membrane for simulation of the blood brain barrier. Incorporation of membranes, electrodes and other elements in PDMS is key to building functionality into microfluidic devices and is a key feature of EFF. Our additively manufactured model will be comprised of brain endothelial cells cultured on a porous membrane (polyester track etch membrane, pores 0.4 µm) sandwiched between two additively manufactured PDMS layers. Human cerebral endothelial cells (hCMEC/D3) will be used, as these cells have been demonstrated to recapitulate key phenotypic characteristics of the BBB such as permeability, expression of junctional proteins and transendothelial electrical resistance. Physiological shear stress will be applied on the cells by flow (~4 Dyn/cm2) to encourage tight junction formation. Demonstration of the blood brain barrier device in Phase I will be followed in Phase II with development of an advanced device. Project summary/abstract

在体外正确模拟体内生物环境通常会导致临床试验的增加成功和更快速地获得有效的治疗是模拟的主要手段。然而，临床和药物实验室研究中的生物环境；微流体技术受到材料和制造挑战的限制。被誉为解决这些挑战的解决方案，但它也面临障碍，例如相对较大的最小特征尺寸和从内部通道去除多余构建材料的难度。制造有潜力构建复杂的 3D 仿生结构并解决以下领域的关键挑战微流体，例如制造高效的混合元件，结合膜或电极，提供集成阀门，并简化微观和宏观尺度之间的连接。然而，微流控领域最有前途、应用最广泛的材料PDMS目前还无法用于 Phase, Inc. 开发了一种名为“增材制造”的专有技术。基于液体介电泳的电场制造 (EFF)，将未固化的 PDMS 成型为规定的形状横截面可以连续固化和粘合以构建 3D 微流体装置。与其他 3DP 模式相比，我们的专利方法提供了对 3D 打印过程的独特控制，以前所未有的分辨率打印弹性材料等新材料的大门，无需后期处理该技术有可能增加 PDMS 微流体的设计空间。更紧密地匹配体内环境，从而实现器官移植等技术的未来进步用于复杂 3D PDMS 微流体设备的增材制造平台的商业化。将使广泛获得 3D 仿生结构成为可能，从而实现更有效的治疗。微流体市场目前价值 140 亿美元，预计到 2027 年将增长到 310 亿美元。 PDMS 基产品约占微流体市场的 30%——市场份额最大。拟议的第一阶段工作将进一步提高增材制造 EFF 工艺的保真度 PDMS 设备通过改进整体平台并具体解决两个目标：该过程的商业可行性的基础第一阶段的工作将 1) 展示功能性。代表性设备的性能和 2) 展示成功整合膜进入微流体装置。第一阶段 SBIR 提案的目标是：目标 1. 在 PDMS 中制造代表性的 3D 微流体装置以展示广泛的实用性。在 EFF 过程中，将在 PDMS 中制造具有两个入口的代表性微流体装置，一个被动入口混合元件、观察/测量通道和出口的成功演示。在 PDMS 设备中增材制造这些基本微流体构件将是制造用于试验研究和进一步商业化的特定设备的点。目标 2. 制造具有集成径迹蚀刻膜的 PDMS 装置，用于模拟血液将膜、电极和其他元件融入 PDMS 中是构建脑屏障的关键。微流体设备的功能是我们的增材制造模型的一个关键特征。由培养在多孔膜（聚酯径迹蚀刻膜、孔 0.4 µm）夹在两个增材制造的 PDMS 层之间。将使用 (hCMEC/D3)，因为这些细胞已被证明能够重现关键表型 BBB 的特征，例如通透性、连接蛋白和跨内皮细胞的表达生理剪切应力将通过流动（~4 Dyn/cm2）施加到细胞上促进紧密连接的形成。随后在第二阶段开发了一种先进的设备。项目概要/摘要