Exosomes are extracellular vesicles (40?100 nm) found in nearly all biological fluids, including blood, urine, saliva, and cerebrospinal fluid. In recent years they have emerged as a potentially powerful tool for biomedical research, biomarker discovery, disease diagnostics, and health monitoring. Exosomes perform diverse cellular functions such as intercellular communication, antigen presentation, and transfer of proteins, mRNA, and miRNA. The proteins found inside of exosomes are characteristic of their cell of origin and many exosomal proteins are linked to diseases such as Alzheimer?s, cancer, and diseases of the kidney, liver, and placenta. Exosomes possess advantages over other circulating biomarkers in that they are highly abundant (thousands to billions per microliter of biofluid), can be collected noninvasively during early stages of disease development, and are very durable, preserving their content through multiple freeze and thaw cycles. While many discoveries have been made in identifying new exosomal protein biomarkers, the difficulties involved in the isolation of exosomes have prevented their widespread use in biomedical research and clinical applications. As a result, there exists a critical need in the research and clinical communities for a simple, rapid, biocompatible, and effective approach for isolating exosomes form biological fluids or in vitro cell culture. In this SBIR project, we will address this unmet need by developing and commercializing acoustofluidic (i.e., the fusion of acoustics and microfluidics) technologies for point-of-care, automated exosome isolation. We name our acoustofluidic exosome-solation technology ExoSOUND. In our Phase-I-type R&D efforts, Ascent has successfully demonstrated the utility and feasibility of the proposed devices by meeting or exceeding the target values of each of the three key parameters identified in the Measures of Success. In Phase II, our commercialization activities will improve performance of the disposable ExoSOUND chips, develop self-contained, beta-testing- ready prototypes, and validate their performance with end users. The proposed ExoSOUND technology will have the following features: 1) Automated exosome isolation, which enables excellent biohazard containment and short processing time (e.g., <20 min to isolate exosomes directly from 100 L undiluted blood), which is significantly less than that of the benchmark technologies (~8 hours); 2) High exosome yield (>82%) in comparison to the benchmark technologies (5?25%); 3) Better ability to isolate biologically active and morphologically intact exosomes than the benchmark technologies; 4) Low driving voltage (<10 V), which simplifies electronics and power requirements; and 5) Low cost (COGS for permanent equipment: <$2,000) in comparison to the benchmark technologies (equipment cost: $50,000?$100,000). With these features, we expect that once demonstrated, the proposed ExoSOUND technology will not only become a more compact, affordable, convenient-to-use replacement to the existing exosome-isolation approaches, but also fulfill many unmet needs in fundamental biomedical research and clinical applications.
Cell-derived vesicles such as exosomes are present in almost all biological fluids. They have been recognized to be valuable for both biomedical research and clinical applications. The proposed project is to develop point-of-care devices that can perform automated, high-yield, high-purity, high-biocompatibility exosome isolation. These devices will help expedite exosome- related biomedical research and aid in the discovery of new exosomal biomarkers.
| Lee, Dong Jun; Mai, John; Huang, Tony Jun (2018) Microfluidic approaches for cell-based molecular diagnosis. Biomicrofluidics 12:051501 |
| Chen, Chuyi; Zhang, Steven Peiran; Mao, Zhangming et al. (2018) Three-dimensional numerical simulation and experimental investigation of boundary-driven streaming in surface acoustic wave microfluidics. Lab Chip 18:3645-3654 |
