High Density 3D Printed Microfluidics With Open Source Resins for Biomedical Applications

用于生物医学应用的采用开源树脂的高密度 3D 打印微流体

• 批准号: 9442402
• 负责人: Gregory P. Nordin
• 金额: $ 41.28万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2020-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9442402
• 关键词: 3-Dimensional; 3D Print; Behavior; Biological; Biological Assay; Biological Markers; Biological Models; Cell Survival; Cells; Characteristics; Coupled; DNA; Data; Detection; Development; Device Designs; Device or Instrument Development; Devices; Dimensions; Drug resistance; Ecosystem; Effectiveness; Equipment; Fluorescence; Formulation; Gene Expression; Genes; Genomic DNA; Genotype; Geometry; Glass; Goals; Health; Hour; Human; Individual; Inflammation; Injection of therapeutic agent; Interferon Type II; Interferons; Lab-On-A-Chips; Light; Lipopolysaccharides; Liquid substance; Measurement; Measures; Medical; Messenger RNA; Methods; MicroRNAs; Microfabrication; Microfluidic Microchips; Microfluidics; Modeling; Molds; Occupations; Optics; Pathogen detection; Performance; Pharmaceutical Preparations; Phenotype; Photosensitivity; Plant Resins; Plasticizers; Plastics; Printing; Proteins; Pump; Reagent; Research; Route; Running; Sampling; Science; Screening for cancer; Silicon; Site; Source; Speed; Structure; System; Techniques; Technology; Testing; Time; Tissue Engineering; base; beta Actin; biomaterial compatibility; cell growth; cost; density; design; digital; drug discovery; exosome; improved; inflammatory marker; innovation; mechanical properties; miniaturize; open source; optical imaging; point-of-care diagnostics; polydimethylsiloxane; polymerization; protein expression; prototype; resistance gene; success; tool; two-dimensional

Project Summary Microfluidics (lab-on-a-chip) is a promising technology for an extremely broad range of biomedical applications including drug discovery; tissue engineering; point-of-care diagnostics; cancer screening based on rare cell detection, protein, DNA, or micro-RNA biomarkers, and more recently, circulating exosomes. This proposal aims to revolutionize the biomedical microfluidic ecosystem by developing 3D printing to routinely create very small, densely integrated microfluidic devices for the biomedical sciences. Such devices are not possible with current microfluidic fabrication techniques, which typically rely on careful alignment and bonding of a handful of individually fabricated layers, each of which has a 2D component layout. In contrast, 3D printing permits all 3 dimensions of the device volume to be fully utilized for component placement and channel routing, offering the opportunity for dense component integration and small device volume (~5 mm3). For example, we include a preliminary device design for a multiplexed cell-based assay that tests both genotype (presence of the relevant gene) and phenotype (cell characteristics and/or behavior) in a device volume of only 2.2 mm × 2.2 mm × 1 mm. The device includes cell growth chambers, monoliths for mRNA capture and fluorescence measurement, and an integrated pump and valves. Moreover, print runs <1 hour enable fast fabrication and test cycles to dramatically speed device development. This proposal intends to initiate a virtuous circle in which 3D printed microfluidics becomes a disruptive tool for biomedical innovation, which should have a substantial impact on human health. To date, the key inhibiting factor for 3D printing has been the inability of commercial 3D printers and resins to fabricate the requisite microvoids that comprise microfluidic structures. Our group recently demonstrated that proper formulation of photosensitive resins coupled with fundamental understanding of the polymerization photophysics enables a low cost commercial stereolithographic (SL) 3D printer to fabricate voids with minimum dimensions on the order of 100 µm. Aims 1 and 2 of this proposal will build on this success by developing a 3D printer and commensurate low cost resins to fabricate valves 40x smaller than what we have already demonstrated, and flow channels with cross section dimensions down to 24 x 30 µm2. These advances will be used in Aim 3 to construct high density microfluidic devices that probe (1) expression of multiple genes in live cells and (2) quantify the viability of those cells in a single device. The overall objective of these studies is to develop 3D printed microfluidic systems with feature dimensions that are enabling for miniaturized cell-based bioanalysis.

项目摘要 微流控（芯片实验室）是一种非常有前途的生物医学技术， 应用包括药物发现;组织工程;床旁诊断;癌症筛查 基于稀有细胞检测、蛋白质、DNA或微RNA生物标志物，以及最近的循环 外来体该提案旨在通过开发3D技术来彻底改变生物医学微流体生态系统。 打印以常规地创建用于生物医学的非常小的、密集集成的微流体装置， 以理工科为重这样的装置对于当前的微流体制造技术是不可能的，该微流体制造技术通常 依赖于少数单独制造的层的仔细对准和粘合，其中每一层都具有 二维元件布局。相比之下，3D打印允许设备体积的所有3个维度完全被打印。 用于元件放置和通道布线，为密集元件提供机会 集成和小器件体积（~5 mm 3）。例如，我们包括一个初步的设备设计， 一种基于细胞的多重检测方法，可检测基因型（相关基因的存在）和表型 (cell在仅2.2 mm × 2.2 mm × 1 mm的器件体积中， 包括细胞生长室、用于mRNA捕获和荧光测量的整料以及 集成泵和阀门。此外，打印运行时间小于1小时，可实现快速制造和测试周期， 大大加快了设备的开发速度。该提案旨在启动一个良性循环，其中3D 打印微流体成为生物医学创新的颠覆性工具，这应该有一个 对人类健康产生重大影响。 到目前为止，3D打印的关键抑制因素是商业3D打印机无法使用， 树脂来制造包括微流体结构的必要的微空隙。我们组最近 证明了光敏树脂的适当配方加上基本的理解 聚合物物理学的发展使低成本的商业立体光刻（SL）3D打印机能够 制造最小尺寸为100 µm的空隙。本提案的目标1和2将 通过开发3D打印机和相应的低成本树脂来制造阀门， 比我们已经展示的小40倍，流道的横截面尺寸 缩小到24 x 30 µm2。这些进展将用于Aim 3，以构建高密度微流体 探测（1）活细胞中多个基因的表达和（2）量化这些基因的存活力的装置 在一个单一的设备中。这些研究的总体目标是开发3D打印微流体 具有特征尺寸的系统能够进行小型化的基于细胞的生物分析。