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US 12,540,297 B2Granted
Microfluidic device for cerebrovascular simulation and high-efficiency blood-brain barrier simulation system comprising same
AssigneeCellartgen Inc.
InventorsSeung Woo Cho, Yong Sun Bahn, Jin Kim, Kyung Tae Lee
Life of this patent
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Abstract
The present disclosure provides a microfluidic device for simulating a blood-brain barrier and a blood-brain barrier simulation system including the same, and the microfluidic device includes: a first channel; a second channel which is adjacently connected to the first channel through one or more microholes and configured to culture neural stem cells; and a chamber which is connected to both ends of the first channel and contains a culture medium.
Claims14
A microfluidic device for simulating a neurovascular unit, comprising:
- a first channel configured to support a fluid flow that generates a shear stress;
- a second channel which is adjacently connected to the first channel through one or more microholes, comprises a hydrogel including collagen and crosslinked or non-crosslinked hyaluronic acid at concentrations sufficient to support three-dimensional differentiation of neural stem cells into astrocytes, and is configured to culture astrocytes and neurons differentiated from neural stem cells in three dimensions;
- a first chamber which is connected to one end of the first channel and comprises a culture medium;
- a second chamber which is connected to another end of the first channel and comprises the culture medium;
- and
- a third channel which is adjacently connected to the second channel and is configured to supply a drug or a nutrient to the second channel,
- wherein the first channel comprises endothelial cells,
- wherein the second channel comprises the astrocytes,
- wherein the astrocytes in the second channel are distributed near the first channel according to a differentiation pattern of the astrocytes, and extend vascular end-feet structures that contact the endothelial cells in the first channel, forming a neurovascular interface that mimics a blood-brain barrier,
- wherein the shear stress generated by the fluid flow in the first channel acts on the endothelial cells so that the endothelial cells, in response to the shear stress, interact with the astrocytes in the second channel to promote distribution of the astrocytes near the first channel,
- wherein the first channel is configured to support a unidirectional flow by a height differential between the first and second chambers, wherein the first and second chambers are open to atmospheric pressure, enabling a controlled flow rate through the first channel that generates a shear stress on the endothelial cells of up to 6 dyne/cm2, and
- wherein the one or more microholes are openings directly connecting the first and second channels.
9 more elements
A complex microfluidic device for simulating other organs than cerebral blood vessel, comprising:
- a first channel configured to support a fluid flow that generates a shear stress;
- a second channel which is adjacently connected to the first channel through one or more microholes, comprises a hydrogel including collagen and crosslinked or non-crosslinked hyaluronic acid at concentrations sufficient to support three-dimensional differentiation of neural stem cells into astrocytes, and is configured to culture astrocytes and neurons differentiated from neural stem cells in three dimensions, and another second channel configured to culture other organ cells;
- a first chamber which is connected to one end of the first channel and comprises a culture medium;
- a second chamber which is connected to another end of the first channel and comprises the culture medium;
- and
- a third channel which is adjacently connected to the second channel and is configured to supply a drug or a nutrient to the second channel,
- wherein the first channel comprises endothelial cells,
- wherein the second channel comprises the astrocytes,
- wherein the astrocytes in the second channel are distributed near the first channel according to a differentiation pattern of the astrocytes, and extend vascular end-feet structures that contact the endothelial cells in the first channel, forming a neurovascular interface that mimics a blood-brain barrier,
- wherein the shear stress generated by the fluid flow in the first channel acts on the endothelial cells so that the endothelial cells, in response to the shear stress, interact with the astrocytes in the second channel to promote distribution of the astrocytes near the first channel,
- wherein the first channel is configured to support a unidirectional flow by a height differential between the first and second chambers, wherein the first and second chambers are open to atmospheric pressure, enabling a controlled flow rate through the first channel that generates a shear stress on the endothelial cells of up to 6 dyne/cm2, and
- wherein the one or more microholes are openings directly connecting the first and second channels.
9 more elements
Dependencies are inferred from the claim text.