Cardiomyocyte containing device, manufacturing method and measuring method
Disclosed is a device ( 100 ) for cardiac electrophysiology screening comprising a substrate ( 10 ) comprising a cavity ( 42 ), said substrate carrying a deformable layer ( 32 ) extending over said cavity ( 42 ), wherein a portion of said deformable layer ( 32 ) covers said cavity and acts as a membrane over said cavity ( 32 ), said portion having a surface comprising a pattern of grooves ( 44 ) and carrying a multi-electrode structure ( 110, 110 ′); and a plurality of cardiomyocytes ( 130 ) assembled in at least some of said grooves ( 44 ). A method of manufacturing such a device ( 100 ) is also disclosed.
1. A device for cardiac electrophysiology screening comprising:
a substrate comprising a cavity, said substrate carrying a deformable layer configured for out-of-plane deformation extending over said cavity such that a central region of the deformable layer is not attached to the substrate, wherein a portion of said deformable layer covers said cavity, said portion having a surface comprising a pattern of grooves that are formed in the deformable layer and extend only partially through the deformable layer, said portion carrying an electrode structure and a fibronectin adhesive coating;
a plurality of cardiomyocytes are configured to spontaneously assemble in an aligned and interconnected fashion into the pattern of grooves on the adhesive-coated surface portion of the deformable layer, such that meaningful readings from coordinated stretch/contraction cycles of the cardiomyocytes may be obtained;
wherein the deformable layer is configured to trigger the assembling of the plurality of cardiomyocytes in the pattern of grooves,
wherein the pattern of grooves have a dimension lower than 200 microns,
wherein the electrode structure is formed in the pattern of grooves or on ridges.
2. The device of claim 1 , wherein each of said grooves has a pair of side walls, each side wall forming a substantially perpendicular angle with the surface of the deformable layer.
3. The device of claim 1 , wherein:
the portion has a circular shape;
the grooves extend radially from the center of the portion to at least one region of the deformable layer covering the substrate; and
the electrode structure comprises at least one spiral electrode.
4. The device of claim 1 , wherein the deformable layer comprises opposite ends, wherein said portion is located along an imaginary axis extending between the opposite ends, said portion separating said opposite ends from each other.
5. The device of claim 4 , wherein said grooves extend in a direction parallel or perpendicular to said axis.
6. The device of claim 4 , wherein the electrode arrangement comprises a plurality of electrodes that over said portion extend in a direction parallel to said axis.
7. The device of claim 1 , wherein the deformable layer is a PDMS layer.
8. The device of claim 1 , wherein:
an edge of the deformable layer on the substrate comprises a tapered protrusion, said protrusion tapering inwards in a direction away from said portion;
the substrate carries a bond pad; and
the device further comprises an interconnection between the electrode structure and the bond pad, said interconnection extending from the portion to the bond pad over the tapered protrusion.
9. An assembly comprising:
a pressure chamber comprising an inlet;
the device of claim 1 , wherein said portion forms a membrane over the pressure chamber; and
a reservoir located over said portion, said pattern of grooves and the electrode structure facing the reservoir.