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Publication Number
US-12680065-B2
Publication Date
2026-07-14
Expiration Date
Abstract
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.
Core Innovation
The invention is an artificial placenta microfluidic device that reconstitutes a maternal-fetal interface by separating a fetal compartment and a maternal compartment with a membrane disposed between first and second microfluidic channels. The membrane provides fluidic communication through the membrane between the first and second microfluidic channels, and the membrane has a first side and a second side.
A first population of cells of a first cell type is encapsulated in a first hydrogel disposed on the first side of the membrane, and a second population of cells of a second cell type is encapsulated in a second hydrogel disposed on the second side of the membrane. The second cell type is differentiated into syncytial structures, establishing a compartmentalized co-culture configuration across the membrane.
The reconstituted interface is used with simulations of physiological or pathological flow conditions to support functional evaluation of placental transfer. The device is configured to support readouts including barrier integrity and transport across the membrane, including syncytial structures, laminin deposition and permeability/transport measurements.
Claims Coverage
The independent claims cover three inventive features: a microfluidic device, fabrication of the microfluidic device, and measuring an amount of a substance of interest using the device.
Membrane-separated microfluidic device with hydrogel-encapsulated cell populations
A microfluidic device comprising a base with first and second microfluidic channels, a membrane disposed between the first and second microfluidic channels such that the channels are adapted for fluidic communication through the membrane, 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.
Fabricating a membrane-separated microfluidic device with hydrogel-encapsulated cell populations
A method of fabricating a microfluidic device comprising fabricating a base having first and second microfluidic channels, disposing a membrane between the first and second microfluidic channels adapted for fluidic communication through the membrane with 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.
Measuring a substance of interest using the syncytial microfluidic device under simulated physiological flow
A method of measuring an amount of a substance of interest comprising providing a microfluidic device with a base having first and second microfluidic channels, a membrane disposed between the channels adapted for fluidic communication through the membrane with 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, and a second population of cells of a second cell type encapsulated in a second hydrogel disposed on the second side, 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.
The inventive approach is a membrane-separated microfluidic device in which two hydrogel-encapsulated cell populations are maintained on opposite sides of the membrane, with the second cell type differentiated into syncytial structures. The same device structure is used in fabrication and in measuring an amount of a substance of interest under simulated physiological flow conditions by quantifying in the two microfluidic channels.
Stated Advantages
Simulates physiological or pathological flow conditions.
Allows measurement of an amount of a substance of interest between the first and second microfluidic channels.
Supports barrier integrity and transport measurements across the membrane.
Reports quantitative transport performance comparable to ex vivo human placenta.
Documented Applications
Using the device to reconstitute a maternal-fetal interface for compartmentalized co-culture and functional evaluation of placental transfer.
Using the device to measure an amount of a substance of interest under simulated physiological flow conditions by monitoring amounts in the first and second microfluidic channels.
Using the device to evaluate syncytial structures and transport-related readouts including permeability/transport measurements.
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