Magnetic Lipid Nanoprobe Platform for Rapid, Highly-Efficient, and Cost-Effective Isolation of Extracellular Vesicles from Non-Invasive Bodily Fluids

SUMMARY/Abstract Extracellular vesicles (EVs) provide a minimally invasive breakthrough pathway for repetitive and multi-omics approach of molecular diagnostics for various diseases such as cardiovascular disease, metabolic disease, cancer, neurologic disease, organ transplantation, pregnancy disorder. EVs, bilayered nano-sized vesicles that are found in most bodily fluids (eg. plasma, serum, urine, saliva, breast milk, cerebrospinal fluid, sweat, ascites fluid, amniotic fluid), are emerging as an appealing type of biomarker for minimally invasive and comprehensive multi-omics (genomics, epigenetics, transcriptomics, proteomics) molecular characterization and diagnosis of diseases. They contain thousands of different proteins, RNA species, and DNA fragments that truly represent the cells of origin. EVs can provide potentially significant benefits for patients who are not accessible for tissue biopsy or need repetitive tissue biopsy. To unleash EVs’ great potential in clinical applications, rapid and efficient isolation of EVs is a prerequisite. However, most of current EVs isolation approaches can’t meet the need in clinical settings due to inherent shortcomings (e.g. lengthy procedure, low yield, and low throughput). In our preliminary study, Captis Diagnostics has developed a new proprietary lipid nanoprobe (LNP) system that can isolate EVs directly from human bodily fluids sample (e.g. blood plasma, serum, saliva and urine) using a rapid workflow and low-cost disposable reagents. To unleash the potential of EVs in multi-omics-based (genomics, epigenetics, transcriptomics, proteomics) disease molecular characterization and diagnosis, we propose to develop and commercialize our proprietary LNP invention for EV isolation from bodily fluids. In this Direct Phase II SBIR, we will further optimize LNP for EV enrichment from bodily fluids, we will focus on EVs isolation from plasma, serum, urine, and saliva in this proposal (Aim 1). In Aim 2, we further will evaluate, validate, and improve the LNP beta prototype as a research kit for EV isolation from plasma, serum, urine, and saliva with end users. Completion of the proposed Phase II will yield four EV isolation kits ready to be delivered to end users. Lipid nanoprobe EV isolation Kit for plasma, Lipid nanoprobe EV isolation Kit for serum, Lipid nanoprobe EV isolation Kit for urine, and Lipid nanoprobe EV isolation Kit for saliva will be launched for sale as a research use only products. This innovative LNP technology platform will facilitate the comprehensive molecular characterization and diagnosis of diseases through multi-omics approaches, including genomics, transcriptomics, and proteomics. Therefore, it will empower extensive basic and translational research in the field of EVs and facilitate the widespread integration of EVs in clinical diagnostics of various human diseases.