Multi-material stereolithographic 3D-printing for prototyping Tissue Chips

用于制作组织芯片原型的多材料立体光刻 3D 打印

• 批准号: 10265548
• 负责人: ALBERT FOLCH
• 金额: $ 18.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-17 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265548
• 关键词: 3-Dimensional; 3D Print; Acrylates; Adsorption; Architecture; Automation; Avidin; Azides; Biotin; Blood Circulation; Cells; Chemistry; Copper; Detection; Development; Devices; Drug Screening; Elasticity; Elements; Excision; Extracellular Matrix; Fluorescein; Functional disorder; Future; Gases; Human; Hydrogels; Hydrophobic Surfaces; Hydrophobicity; Immobilization; In Vitro; Liquid substance; Metals; Methacrylates; Methods; Microfluidic Microchips; Microfluidics; Molecular; Organ; Organoids; Outcome; Pattern; Permeability; Pharmaceutical Preparations; Physiology; Plant Resins; Polymers; Printing; Property; Protocols documentation; Resolution; Scheme; Shapes; Structure; Surface; Tissue Microarray; Tissues; Triazoles; absorption; aqueous; base; biofabrication; biomaterial compatibility; bioprinting; cancer cell; cell type; design; experimental study; flexibility; force sensor; human tissue; innovation; lithography; organ on a chip; poly(dimethylsiloxane); poly(ethylene glycol)diacrylate; prototype; scaffold; screening; sensor

PROJECT SUMMARY / ABSTRACT Tissue Chips – microfluidic devices containing human cells in 3D architectures that attempt to recapitulate the physiology and pathophysiology of human tissues and organs – contain advanced designs that critically require 3D/modular fabrication, the incorporation of multiple materials and functionalities, and fluidic automation. The vast majority of Tissue Chips are still prototyped in poly(dimethylsiloxane) (PDMS). However, difficult barriers remain for PDMS as a Tissue Chip material. The surface of PDMS is porous and hydrophobic, so both absorption into PDMS and adsorption onto PDMS can potentially alter experimental outcomes by changing the target concentrations and by partitioning molecules in undesired regions of a microfluidic device. 3D-Printing holds an obvious potential for Tissue Chips. Stereolithography (SL), in particular, has been an excellent choice for modulating shapes in 3D at high resolution but modulating material composition is still a challenge. There is a critical need for more advanced, high-resolution and multi-material SL-printing approaches to building future Tissue Chips that can integrate the structural components of a device (channels and valves) with biofabrication (cells and scaffolds). Yet there is no off-the-shelf solution to SL-print multi-material microfluidic devices of wide applicability. This application proposes the synthesis and SL-printing of cyclo-octyne methacrylate (COMA) resin, which will enable the immobilization of any biomolecule-azide of choice onto the COMA-printed surfaces. COMA for derivatizing printed parts via straightforward copper-free (biocompatible) click chemistry, in this case by conjugation to an azide group which spontaneously and specifically reacts with the COMA group in aqueous solutions. Using biotin-azide (commercially available) and an avidin linkage, we will be able to immobilize any biotinylated biomolecule of choice onto the COMA-printed surfaces. We will also use a baseline acrylate resin composed of poly(ethylene glycol) diacrylate (MW~258) (PEG-DA-258), which has successfully been used in microfluidics by several labs, and will experiment with blending PEG-DA-258 with other diacrylates and/or monoacrylates to obtain resins with differing properties, such as higher flexibility. To print devices that are made partially with PEG-DA-258 resin (or blends) and partially with COMA resin (or blends), we will utilize a strategy for co-printing multiple acrylate resins recently utilized by the Folch lab that consists of pausing the print and exchanging the resins in the vat. This scheme will have wide applicability to 3D-print microfluidic devices with multiple regions bearing molecular functionalities (e.g. biomolecular detection, cell capture) and/or elements with distinct sensing/actuating properties (e.g. microvalves, force sensors, etc.). Examples include 3D-printed multiplexed immunosensors based on COMA-derivatized regions, cell trapping devices for drug screening, and organoid-on-a-chip automated platforms, among others.

项目摘要 /摘要 组织芯片 - 在3D体系结构中含有人类细胞的微流体设备，试图概括 人体组织和器官的生理学和病理生理学 - 包含批判性需要的高级设计 3D/模块化制造，多种材料和功能的结合以及流体自动化。 绝大多数组织芯片仍在聚（二甲基硅氧烷）（PDMS）中进行原型。但是，困难 作为组织芯片材料，PDM的障碍仍然存在。 PDM的表面是多孔和疏水的，因此 抽象为PDMS，并在PDM中添加吸附可以通过改变来改变实验结果 靶浓度和通过微流体设备不希望区域的分子进行划分。 3D打印具有组织芯片的明显潜力。尤其是立体光刻学（SL） 在高分辨率下以3D调制形状的绝佳选择，但调节材料组成仍然是 挑战。迫切需要更高级，高分辨率和多物质SL印刷 构建可以整合设备（通道）结构组件的未来组织芯片的方法 带有生物制作的阀（细胞和支架）。然而，没有现成的解决方案用于SL-PRINT多物质 具有广泛适用性的微流体设备。 该应用提出了环甲丙烯酸酯（昏迷）树脂的合成和SL印刷 将使任何选择的生物分子 - 亚齐德固定在昏迷的表面上。 通过直接无铜（生物相容性）衍生印刷零件的昏迷点击化学，在这种情况下 通过与叠氮化基团的共轭，该基团发起了昏迷，并专门与昏迷组反应 解决方案。使用生物素 - 氮化物（市售）和Avidin连接，我们将能够固定任何 选择的生物素化生物分子在昏迷的表面上。我们还将使用基线丙烯酸树脂 由聚（乙二醇）二丙烯酸酯（MW〜258）（PEG-DA-258）组成，已成功地用于 通过几个实验室的微流体，并将尝试将PEG-DA-258与其他二氧化碳和/或 单丙烯酸酯获得具有不同特性的树脂，例如较高的柔韧性。打印制造的设备 部分与PEG-DA-258树脂（或混合），部分与昏迷树脂（或混合），我们将利用策略 对于Folch Lab最近使用的多个丙烯酸树脂的共同印刷，该树脂包括暂停印刷品和 在增值税中交换树脂。该方案将对3D-PRINT微流体设备具有广泛的适用性 带有分子功能（例如生物分子检测，细胞捕获）和/或元素的多个区域 独特的感应/致动特性（例如，微欧洲，力传感器等）。示例包括3D打印 基于昏迷区域的多重免疫传感器，用于药物筛查的细胞诱捕装置， 芯片上的器官自动化平台等。