Scalable Isolation of Therapeutic Bio-nanoparticles Using Microhydrocyclones

使用微水力旋流器大规模分离治疗性生物纳米颗粒

• 批准号: 1950234
• 负责人: Don DeVoe
• 金额: $ 37.7万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1950234&HistoricalAwards=false
• 关键词: Scalable; Isolation; Therapeutic; Bio; nanoparticles

This grant supports research on a manufacturing technique for the scalable production of drugs based on biological nanoparticles, promoting the progress of science, advancing national prosperity and improving human health. The research involves fabricating a new class of miniature devices called microhydrocyclones using a three-dimensional printing process. Three-dimensional printing or additive manufacturing is used to create three-dimensional structures with exceptionally high resolution, resulting in features one thousand times smaller than the diameter of a human hair. Microhydrocyclones are microfluidic devices that permit the rapid isolation or separation of biological nanoparticles called exosomes. Exosomes have emerged as highly promising vehicles for targeted drug delivery in personalized medicine. But existing processing methods are too slow to support effective and high throughput drug development. This project is a fundamental study in the manufacture of high-performance microhydrocyclone devices and their application in high throughput exosome separation and collection. The research bridges the fields of manufacturing, microsystems technology and bioengineering. The results of this effort have broad impacts beyond drug development where rapid nanoparticle separations are needed, including the chemical, energy, and biomedical industries, which benefits the U.S. economy. The project expands participation of underrepresented groups and women and introduces K-12 students to research for a positive impact on engineering education.Exosomes are cell-secreted bio-nanoparticles. Exosomes offer enormous potential for targeted nanotherapeutic delivery, but improved isolation techniques are needed to provide the required processing throughput for drug development. This research studies a novel microhydrocyclone technology, which is capable of increasing the throughput of exosome separations by orders of magnitude over existing methods. The microhydrocyclone design is guided by computational fluid dynamics (CFD) modeling. The team develops and validates an analytical scaling model of the miniature hydrocyclone separation process. It leverages nanoscale laser direct writing to integrate functional microhydrocyclone devices within thermoplastic microfluidic substrates. A multi-element bandpass concentrator design is developed for size-selective exosome collection. To reduce risk, several features are added to the device such as coating with silica to make it leak-free. The performance of the technology for continuous-flow isolation of exosomes from cell culture supernatant is assessed.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该赠款支持对基于生物纳米颗粒的药物可扩展生产的制造技术的研究，促进科学的进步，促进国家繁荣并改善人类健康。该研究涉及使用三维印刷过程制造新的称为微氢化环酮的微型设备。 三维印刷或添加剂制造用于创建具有异常高分辨率的三维结构，导致比人毛直径小1000倍。微水合细胞是微流体设备，允许快速分离或分离称为外泌体的生物纳米颗粒。外泌体已成为具有个性化药物的有针对性药物的高度有前途的车辆。但是现有的加工方法太慢，无法支持有效和高吞吐药物开发。该项目是一项基础研究，用于制造高性能微水合细胞设备及其在高吞吐量外泌体分离和收集中的应用。该研究桥接了制造，微系统技术和生物工程领域。这项工作的结果超出了药物开发的广泛影响，在药物开发之外，需要快速的纳米颗粒分离，包括有利于美国经济的化学，能源和生物医学行业。该项目扩大了代表性不足的群体和妇女的参与，并介绍了K-12学生对工程教育产生积极影响的研究。外观是细胞分泌的生物纳米粒子。外泌体为靶向纳米疗法提供了巨大的潜力，但是需要改进的隔离技术来为药物开发提供所需的加工吞吐量。这项研究研究了一种新型的微水合细胞技术，能够通过与现有方法相比，通过数量级来增加外泌体分离的吞吐量。微水合细胞设计以计算流体动力学（CFD）建模为指导。 该团队开发并验证了微型氢核分离过程的分析缩放模型。它利用纳米级激光直接写入来整合热塑性微流体底物中的功能性微水合物设备。开发了多元素的带通浓缩器设计，用于尺寸选择性外泌体收集。为了降低风险，将几个功能添加到设备中，例如与二氧化硅涂层，以使其无泄漏。评估了从细胞培养的上清液中连续流隔离外泌体的技术的性能。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来获得支持。