Artificial placenta and methods of preparation
The presently disclosed subject matter provides a microfluidic device that can simulate capillary blood flow on a fetal side of the device and pooled blood on a maternal side of the device (i.e., intervillous space). The microfluidic device can reconstitute the maternal-fetal interface, can expand the capabilities of cell culture models, and can provide an alternative to current maternal-fetal transfer models.
1 . A microfluidic device comprising:
a base, having first and second microfluidic channels disposed thereon;
a membrane disposed between the first and second microfluidic channels such that the first and second microfluidic channels are adapted for fluidic communication through the membrane, the membrane having a first side and a second side;
a first population of cells of a first cell type encapsulated in a first hydrogel disposed on the first side of the membrane; and
a second population of cells of a second cell type encapsulated in a second hydrogel disposed on the second side of the membrane, wherein the second cell type is differentiated into syncytial structures.
2 . The microfluidic device of claim 1 , wherein the second cell type comprises choriocarcinoma cells.
3 . The microfluidic device of claim 1 , wherein the first population of cells or the second population of cells further comprises white blood cells.
4 . The microfluidic device of claim 1 , wherein the membrane comprises a porous polycarbonate membrane.
5 . The microfluidic device of claim 1 , wherein the membrane is coated with an extracellular matrix.
6 . The microfluidic device of claim 1 , wherein the membrane comprises one of a polyester membrane, a polytetrafluoroethylene membrane, a paper membrane, an elastomeric membrane, or an extracellular matrix membrane.
7 . The microfluidic device of claim 1 , wherein one of the first population of cells or the second population of cells further comprises an artificially induced pathology.
8 . The microfluidic device of claim 1 , wherein at least one of the first hydrogel and the second hydrogel is a collagen gel.
9 . The microfluidic device of claim 1 , further comprising an additional population of cells of a third cell type.
10 . The microfluidic device of claim 9 , wherein the additional population of cells is encapsulated in one or more of the first hydrogel and the second hydrogel.
11 . The microfluidic device of claim 9 , wherein the third cell type comprises one of Hofbauer cells and fibroblasts.
12 . The microfluidic device of claim 9 , wherein the third cell type comprises an artificially induced pathology.
13 . A method of fabricating a microfluidic device comprising:
fabricating a base, the base having first and second microfluidic channels disposed thereon;
disposing a membrane between the first and second microfluidic channels such that the first and second microfluidic channels are adapted for fluidic communication through the membrane, the membrane having a first side and a second side;
growing a first population of cells of a first cell type within a first hydrogel disposed on the first side of the membrane; and
growing a second population of cells of a second cell type within a second hydrogel disposed on the second side of the membrane,
wherein the second cell type is differentiated into syncytial structures.
14 . The method of claim 13 , wherein one of the first population of cells or the second population of cells further comprises an artificially induced pathology.
15 . The method of claim 13 , wherein at least one of the first hydrogel and the second hydrogel is a collagen gel.
16 . A method of measuring an amount of a substance of interest, comprising:
providing a microfluidic device having
a base, having first and second microfluidic channels deposed thereon;
a membrane disposed between the first and second microfluidic channels such that the first and second microfluidic channels are adapted for fluidic communication through the membrane, the membrane having a first side and a second side;
a first population of cells of a first cell type encapsulated in a first hydrogel disposed on the first side of the membrane; and
a second population of cells of a second cell type encapsulated in a second hydrogel disposed on the second side of the membrane, wherein the second cell type is differentiated into syncytial structures;
placing the substance of interest in one of the first or second microfluidic channels;
simulating physiological flow conditions; and
measuring the amount of the substance of interest in the first and second microfluidic channels.
17 . The method of claim 16 , wherein the substance of interest is one of glucose, amino acids, proteins, or small molecule pharmaceuticals.
18 . The method of claim 16 , wherein the substance of interest is labeled with fluorescent molecules, and wherein the measuring the amount of substance of interest comprises measuring an amount of fluorescence.
19 . The method of claim 16 , wherein one of the first or second population of cells further comprises an artificially induced pathology.
20 . The method of claim 16 , wherein at least one of the first hydrogel and the second hydrogel is a collagen gel.