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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.

Cytokines are a broad category of intercellular signaling proteins that are critical for intercellular communication in human health and disease. However, systematic profiling of cytokine signaling activities has remained challenging due to the short half-lives of cytokines, and the pleiotropic functions and redundancy of cytokine activities within specific cellular contexts.

The tumor microenvironment (TME) is a complex mixture of cell types whose interactions affect tumor growth and clinical outcome. Recent studies using fluorescence-activated cell sorting (FACS) and single-cell RNA sequencing (RNAseq) to elucidate tissue composition and cell-cell interactions in the TME led to improved biomarkers of patient response and new treatment opportunities. However, the use of FACS is limited to simultaneously measuring the expression of a few protein markers, whereas the use of single-cell RNAseq has been limited due to cost and scarcity of fresh tumor biopsies.

Topoisomerase enzymes play an important role in cancer progression by controlling changes in DNA structure through catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Therefore, topoisomerases are important targets for cancer chemotherapy. Many topoisomerase 1 (TOP1) inhibitors such as camptothecin, rinotecan, and topotecan are widely used anti-cancer agents that work by stabilizing the TOP1-DNA cleavage complex.