Organs-on-chips as a platform for epigenetics discovery
Inventors
Karalis, Catherine • Kujala, Ville
Assignees
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Publication Number
US-12036548-B2
Publication Date
2024-07-16
Expiration Date
Abstract
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.
Core Innovation
The invention provides an organs-on-chips epigenetics platform using a microfluidic device with at least one microfluidic channel comprising endothelial cells. The platform contacts biological samples including extracellular vesicles obtained from a human with disease or condition, with the endothelial cells under conditions that create one or more exposed cells.
The exposed cells are interrogated by detecting cell injury changes and/or detecting a change in the one or more exposed cells, wherein the change comprises increased permeability of the endothelial cells. The platform is configured to create exposure-specific signatures by profiling epigenetic effects associated with the extracellular vesicle exposure, including chromosome state/uptake effects and DNA/chromosome modifications.
The platform compares epigenetic profiles across experimental conditions and controls and uses baseline signature panels or a database comparison for diagnostics and forensics. Effluent is collected as a “virtual blood draw,” supporting downstream comparison against stored baseline panels or database signatures.
Claims Coverage
The consolidated content identifies two independent method claims. Each independent claim centers on a microfluidic device with endothelial cells, exposure to extracellular vesicles obtained from a human patient with disease or condition, and detection of an endothelial response.
Endothelial-cell microfluidic channel for EV exposure
Providing a microfluidic device comprising at least one microfluidic channel, said microfluidic channel comprising endothelial cells of a first tissue.
Extracellular vesicles obtained from a human disease source
Providing a plurality of extracellular vesicles obtained from a human with a disease of a second tissue.
Controlled exposure of endothelial cells to extracellular vesicles
Introducing said extracellular vesicles into said microfluidic channel under conditions wherein said endothelial cells are exposed to said extracellular vesicles so as to create one or more exposed cells.
Detecting cell injury change in exposed endothelial cells
Detecting a cell injury change in said one or more exposed cells.
Extracellular vesicles obtained from a patient with disease or condition
Providing a plurality of extracellular vesicles obtained from a human patient, said human patient having a disease or condition.
Detecting increased permeability of endothelial cells
Detecting a change in said one or more exposed cells wherein said change comprises increased permeability of said endothelial cells.
Overall, the claim set covers microfluidic device-based endothelial-cell exposure to extracellular vesicles obtained from humans with disease or condition, coupled to detecting either a cell injury change or increased endothelial permeability.
Stated Advantages
Enables detection of a cell injury change in exposed endothelial cells.
Enables detection of increased permeability of endothelial cells after exposure to extracellular vesicles.
Supports generating exposure-specific epigenetic signatures and comparing profiles across experimental conditions and controls for diagnostics and forensics.
Documented Applications
Use for diagnostics and forensics via baseline signature panels or database comparisons using exposure-specific epigenetic signatures collected via effluent as a “virtual blood draw”.
Assessment of disease-related effects using extracellular vesicles obtained from a human with disease, including endothelial cell exposure and measurement of cell injury change and/or increased permeability.
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