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.
