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Extracellular vesicles (EVs) are lipid bilayer-enclosed particles that are released from cells. EVs may contain proteins derived from their cells of origin with the potential as diagnostic biomarkers indicating the state of the cells when released. However, due to their small size (50-1000nm), the methods currently used to phenotype EVs have limited sensitivity and scale. A need exists for development of novel technologies improving EV detection and phenotyping.

Immunotherapy is a cutting-edge new category of treatment that aims to harness and, in some cases, modify the patient’s own immune cells to improve their ability to cure diseases. It can be an effective approach for a variety of conditions, ranging from cancer to inflammatory diseases.  However, a number of obstacles to the overall success of immunotherapy still exist.  For example, reactivity against a target antigen can be attenuated or the lifespan of the “modified” immune cells can be too short.

Measuring and mapping nervous tissue microstructure noninvasively is a long sought-after goal in neuroscience. Clinically, several neuropathologies such as cancer and stroke, are associated with changes in tissue microstructure. Diffusion tensor imaging (DTI), which models diffusion anisotropy, is an ideal imaging modality to elucidate these changes. However, DTI provides a mean diffusion tensor averaged over the entire MRI voxel. This has limitations when applied to heterogeneous neural tissue.

There are no effective treatments for Alzheimer’s disease (AD), a progressive brain disease that slowly destroys a person’s memory, cognitive skills and ability to carry out the simplest tasks. AD affects more than 5 million individuals in the United States and ranks as the sixth leading cause of death. The ε4 allele of the apolipoprotein-E (APOE) gene is the strongest genetic risk factor for sporadic or late-onset AD. Heterozygous carriers of the ε4 allele are at three-to-four times greater risk; homozygous carriers are at ten times greater risk.

Multi-parameter flow cytometry has been extensively used in multiple disciplines of biological discoveries, including immunology and cancer research. However, the disadvantage of traditional flow cytometry platforms using excitation lasers and fluorescence detectors is spectral overlap when using multiple dyes on the same biological sample. Metaethical compensation of spectral overlap could only be effective to a certain degree. Mass cytometry is advantageous compared to flow cytometry but is pricey and requires highly skilled operators. 

Biological nanoparticles, like extracellular vesicles (EVs), possess unique biological characteristics making them attractive therapeutic agents, targets, or disease biomarkers. However, their use is hindered by the lack of tools available to accurately detect, sort, and analyze. Flow cytometers are used to sort and study individual cells. But, they are unable to detect and sort nanomaterials smaller than 200 nanometers with single epitope sensitivity.

Extracellular Vesicles (EVs), including exosomes and microvesicles, are nanometer-sized membranous vesicles that can carry different types of cargos, such as proteins, nucleic acids and metabolites. EVs are produced and released by most cell types. They act as biological mediators for intercellular communication via delivery of their cargos. This unique ability spurred translational research interest for targeted delivery of therapeutic molecules to treat a wide range of diseases. EVs also contain interesting information of their specific cellular origin.

Traumatic brain injury (TBI) represents a major medical, social and economic concern worldwide due to significant mortality – especially among younger populations – and long-term disabilities. Various pathological brain lesions (e.g., intracerebral bleedings, necrotic-ischemic lesions, tissue avulsion) are produced by impacting mechanical forces. Among these, diffuse axonal injury (DAI) is one of the most significant brain lesions typically associated with trauma. However, DAI is not necessarily linked with TBI exposure. Therefore, the term “traumatic axonal injury (TAI)” is commonly used.

There is no known cure for Alzheimer’s disease, a brain disorder that severely affects memory, thinking, learning, and organizing skills. It eventually decreases a person’s ability to carry out simple, daily activities. It is predicted that over 14 million Americans will develop Alzheimer’s without effective treatment options. Mild cognitive impairment (MCI) is a stage prior to Alzheimer’s when memory problems become noticeable. A patient’s ability to function and live independently remain intact as the brain compensates for disease-related changes.

Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. Ephrin (Eph) receptors are a clinically relevant class of receptor tyrosine kinases. Related signaling pathways are associated with oncogenesis of a number of cancers. NCI investigators found that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells.