Organs-on-chips as a platform for epigenetics discovery
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.
1. A method comprising:
a) providing a microfluidic device comprising at least one microfluidic channel, said microfluidic channel comprising endothelial cells of a first tissue; and
b) providing a plurality of extracellular vesicles obtained from a human with a disease of a second tissue;
c) 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; and
d) detecting a cell injury change in said one or more exposed cells.
2. The method of claim 1 , further comprising flowing media at a flow rate through said microfluidic channel prior to step c).
3. The method of claim 2 , wherein said extracellular vesicles are introduced by adding them to said flowing media.
4. The method of claim 1 , wherein said human patient has a heart condition.
5. A method comprising:
a) providing a microfluidic device comprising at least one microfluidic channel, said microfluidic channel comprising endothelial cells; and
b) providing a plurality of extracellular vesicles obtained from a human patient, said human patient having a disease or condition;
c) 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; and
d) detecting a change in said one or more exposed cells wherein said change comprises increased permeability of said endothelial cells.
6. The method of claim 5 , further comprising flowing media at a flow rate through said microfluidic channel prior to step c).
7. The method of claim 5 , wherein said human patient has a heart condition.
8. The method of claim 5 , wherein said permeability is increased in comparison to endothelial cells exposed to extracellular vesicles obtained from a healthy human patient.