Scalable Isolation of Therapeutic Bio-nanoparticles Using Microhydrocyclones

该基金支持基于生物纳米颗粒的可扩展药物生产制造技术的研究，促进科学进步，促进国家繁荣，改善人类健康。这项研究包括使用三维打印工艺制造一种新型的微型装置，称为微型旋流器。三维打印或增材制造用于创建具有极高分辨率的三维结构，其特征比人类头发的直径小1000倍。微水力旋流器是一种微流体装置，可以快速分离或分离被称为外泌体的生物纳米颗粒。外泌体已成为个性化医疗中靶向药物输送的极具前景的载体。但现有的加工方法太慢，无法支持有效和高通量的药物开发。本课题是高性能微旋流器的研制及其在高通量外泌体分离和收集中的应用的基础性研究。该研究跨越了制造、微系统技术和生物工程领域。这一努力的结果具有广泛的影响，超出了需要快速分离纳米颗粒的药物开发，包括化学，能源和生物医学行业，这有利于美国经济。该项目扩大了代表性不足的群体和妇女的参与，并引入K-12学生进行研究，以对工程教育产生积极影响。外泌体是细胞分泌的生物纳米颗粒。外泌体为靶向纳米治疗递送提供了巨大的潜力，但需要改进的分离技术来提供药物开发所需的处理吞吐量。本研究研究了一种新型的微水力旋流器技术，该技术能够将外泌体分离的吞吐量提高到现有方法的数量级。微旋流器的设计以计算流体力学（CFD）模型为指导。该团队开发并验证了微型水力旋流器分离过程的分析缩放模型。它利用纳米级激光直接写入集成热塑性微流体基板内的功能微水力旋流器装置。开发了一种多元素带通浓缩器设计，用于大小选择性外泌体收集。为了降低风险，在设备中添加了一些功能，例如用二氧化硅涂层使其无泄漏。对细胞培养上清液连续流式分离外泌体技术的性能进行了评价。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.