Multiplexed Profiling of Single Extracellular Vesicles

Extracellular vesicles (EV) are a family of cell-originating, membrane-enveloped nanoparticles with diverse biological function, diagnostic potential, and therapeutic applications. While EV can be abundant in circulation, their small size (∼4 order of magnitude smaller than cells) has necessitated bulk analyses, making many more nuanced biological explorations, cell of origin questions, or heterogeneity investigations impossible. Here we describe a single EV analysis (SEA) technique which is simple, sensitive, multiplexable, and practical. We profiled glioblastoma EV and discovered surprising variations in putative pan-EV as well as tumor cell markers on EV. These analyses shed light on the heterogeneous biomarker profiles of EV. The SEA technology has the potential to address fundamental questions in vesicle biology and clinical applications

Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection

Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting