Provided herein are methods of determining whether an extracellular vesicle (EV) can cross an endothelial barrier (e.g., the blood brain barrier). In some embodiments, the EV originates from a cancer cell. In some embodiments, the cancer has a higher likelihood of metastasizing (to the brain) if the EV originating from a cancer cell is determined to be able to cross an endothelial barrier (e.g., the blood brain barrier). Thus, further provided herein are methods of determining whether a subject who has cancer is likely to develop metastatic cancer. In some embodiments, the subject is treated for the metastatic cancer accordingly.

The present invention relates to the identification of ALMS1 as the missing player involved in the regulation of the insulin-mediated glucose uptake through GLUT4 sorting vesicles, and to the down-regulation of ALMS1 by PKC. Accordingly, the present invention relates to a molecule capable of preventing the binding of PKC on ALMS1 for use for treating or preventing diabetes, in particular type 2 diabetes. In addition, the present invention relates to a method for identifying molecule capable of preventing the binding of PKC on ALMS1.

Disclosed herein are embodiments of devices for managing fluid transport. In particular disclosed embodiments, the devices are used to manage fluid transport in reactor systems, such as bio-assessment systems, chemical synthesis reactors, and the like. The devices disclosed herein include fluid management devices, reservoir assemblies, valving systems, pumps, and combinations thereof. The devices disclosed herein are cost-efficient and user-friendly and can be implemented in a variety of reactor systems.

Provided is a method for inducing differentiation into conjunctival epithelial cells, conjunctival goblet cells, and conjunctival epithelial stem and progenitor cells, the method comprising culturing colonies of pluripotent stem cells in a medium containing an epidermal growth factor (EGF) signaling activator to induce differentiation of the pluripotent stem cells. The present invention enables differentiation of pluripotent stem cells including iPS cells into conjunctival epithelial cells, conjunctival goblet cells, and conjunctival epithelial stem and progenitor cells and therefore is very useful for, for example, basic research on conjunctival epithelial cells and conjunctival goblet cells, regenerative therapy for intractable ocular surface diseases, and research related to the diseases.

Disclosed herein is a method for assessing a compound interacting with a target on polarized epithelial cells. The method comprising the steps of providing an organ chip comprising a main channel and polarized epithelial cells, wherein the main channel is divided into an apical channel and a basal channel separated by the polarized epithelial cells, wherein the apical side of the polarized epithelial cells is directed towards the apical channel and the basolateral side of the polarized epithelial cells is directed towards the basal channel. Determining the localization and optionally the expression level of the target on the polarized epithelial cells. Administering the compound and optionally immune cells, preferably peripheral blood mononuclear cells (PBMC) to the basal channel, when the target is localized on the basolateral side of the epithelial cells or administering the compound and optionally immune cells, preferably peripheral blood mononuclear cells (PBMC) to the apical channel, when the target is localized on the apical side of the epithelial cells. Measuring a parameter of the administration of the compound and the peripheral blood mononuclear cells.

The present invention relates to microfluidic fluidic devices, methods and systems for use in identifying epigenetic signatures in a range of sample types, e.g., cells established on a chip (including but not limited to single cell samples, cell populations, C cell layers and whole tissues, such as a biopsy), immune cells, cfDNA, exosomes, and the like. More specifically, in some embodiments, a microfluidic chip containing a sample is contacted with a test compound (e.g. DNA altering test compound, an RNA expression altering test compound, etc.) for use in providing a diagnostic epigenetic signature for that type of sample (or cell type) exposed to that specific test compound. In some embodiments, after contact with a test compound, effluent fluids (e.g. fluids exiting the chip that contacted the cells) are derived for testing as a virtual blood draw. In some embodiments, epigenetic signatures include (but are not limited to) identifying specific combinations of modifications of chromosomes and specific modifications of DNA.

The present invention provides a method for screening for a compound that is effective against disorders of the corneal endothelium. The method according to the present invention comprises: (a) a step for bringing candidate compounds into contact with immortalized cells of Fuchs' corneal endothelial dystrophy in the presence of transforming growth factor (TGF)-, making evaluations on the inhibitory activity of said candidate compounds against said TGF-, and selecting a compound having the inhibitory activity; (b) a step for evaluating the toxicity of the compound selected in step (a) with respect to said immortalized cells; (c) a step for evaluating the inhibitory activity of the compound selected in step (a) against said TGF-; and (d) a step for selecting a compound that has been evaluated to have low toxicity to said immortalized cells in step (b) and has been evaluated to have inhibitory activity against said TGF- in step (c). The method according to the present invention makes it possible to screen for a compound that is effective for disorders of the corneal endothelium.

The present invention is related to the field of liver disease. Solid substrates comprising microfluidic channels (e.g., microchips) are configured to support growing and differentiating hepatocytes and are contemplated to provide a suitable environment for the development of fully functional liver tissue. These solid substrates can be used to induce various toxicity conditions in the liver tissue subsequent to the exposure to various chemicals. For example, chronic exposure to ethanol induces a clinical state of alcoholic liver disease in the liver tissue. Alternatively, certain disease states can result in the development of non-alcoholic liver diseases (e.g., non- alcoholic steatohepatitis; NASH).

This disclosure provides a method for measuring coagulation of blood or plasma samples using viscoelastic tests (VET) wherein the measuring is performed in the presence of immobilised endothelial cells.

The present invention contemplates compositions, devices and methods of simulating biological fluids in a fluidic device, including but not limited to a microfluidic chip. In one embodiment, fluid comprising a colloid under flow in a microfluidic chip has a fluid density or viscosity similar to a bodily fluid, e.g. blood, lymph, lung fluid, or the like. In one embodiment, a fluid is provided as a Theologically biomimetic blood surrogate or substitute for simulating physiological shear stress and cell dynamics in fluidic device, including but not limited to immune cells.