A nanosized magnetic particle system for fast and efficient neuronal extracellular vesicle enrichment from plasma

SUMMARY/Abstract Extracellular vesicles (EVs) are nanovesicles, which contain surface markers, and cell- and cell-state-specific cargo of their tissue (and cell) of origin, reflecting the tissue or cell’s physiological state. Most importantly, neuronal EVs can pass the blood-brain barrier (BBB) into blood circulation and provide a new approach of gaining direct access to brain pathogenic processes. Emerging clinical studies show that neuronal EVs in blood carry pathogenic biomarkers that can detect and predict neurological diseases such as, Alzheimer’s disease, Parkinson disease, amyotrophic lateral sclerosis, and traumatic brain injury, etc. Therefore, enrichment of neuronal EVs from peripheral blood provides a minimally invasive way to sample components of brain tissue for neurological diseases. To unleash neuronal EVs’ great potential in neurological diseases diagnosis applications, rapid and efficient enrichment of neuronal EVs from blood plasma is a prerequisite. However, there is major challenge to efficiently isolate neuronal EVs from blood plasma, and there are no commercially available technologies/kits for the isolation of neuronal EVs from blood plasma. Herein, we propose to develop a neuronal EVs nanoprobes (neuron-NPs) technology for high-yield isolation of neuronal EV directly from plasma sample as a research use only kit. We will develop and optimize these neuron- NPs for rapid and efficient magnetic isolation of neuronal EVs in a buffer system (Aim 1). The Aim 2 will perform analytical validation of neuron-NP technology in plasma samples. Successful completion of these Aims will yield an advanced proprietary technology platform for neuronal EVs isolations in basic and clinical research for various neurological diseases. Phase II activities will be focused on scaling up the manufacturing of neuronal EVs nanoprobes kit and developing high-throughput automatic sample processing system integrated with neuron- NPs kit.