Nanopore Array for Multiparameter Analysis of Single Extracellular Vesicles

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Project Summary Today, researchers and clinicians, in academia and industry, lack the tools and technologies needed to accurately characterize, differentiate, and sort extracellular vesicles (EVs); currently available technologies were simply not developed to characterize entities smaller than 200 nanometers in size. While the importance of EVs in directing cargo delivery for intercellular communication is well known, the inability to profile the true distribution of their biophysical properties is the main hindrance to understanding the mechanisms of action, identifying disease-specific biomarkers, and harnessing the therapeutic potential of EV-based nanomedicine. During this Phase I STTR program, Electronic BioSciences (EBS), a company with a successful track record of commercializing nanopore-based analytical technology and the associated high-performance, low-noise electronics, will collaborate with Distinguished Professor Henry S. White at the University of Utah, who is a foremost expert in nanopores, mass transport and electroanalytical characterization, to develop and demonstrate an entirely new technology capable of state-of-the-art, comprehensive EV characterization and sample profiling at the single-vesicle level. Furthermore, the ability to quickly assess individual EVs will enable the ability to sort and isolate specific EV subpopulations for further downstream characterization and/or utilization. During this project, a prototype system will be built and the feasibility of comprehensively characterizing and sorting/isolating specific EV populations will be demonstrated and validated. The resulting system will have the ease-of-use, throughput, and price point of a high-throughput, “low-resolution” flow-cytometer, but the resolution of state-of- the-art microscopy techniques, such as scanning or transmission electron microscopy (SEM or TEM, respectively) or atomic force microscopy (AFM). The advantage of the proposed technology will be the development of a system enabling the ability to identify and sort/isolate precisely defined populations of biological- and medical-significance nanoscale (<200 nm) entities using high-dimensional (multiparameter) data, which will have applications far beyond EVs, including but not limited to characterizing other nanostructures important in drug delivery and gene therapy nanomedicines such as lipid nanoparticles for vaccines, exosome- based therapeutics, lentivirus, virus-like particles, and polymer-based nanocapsules. Thus, the successful completion of this program will result in a broadly applicable tool able to bring precision to bear on these smallest of couriers and enable the characterization/classification urgently needed to advance the fields of EVs and nanomedicine.