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Publication Number
US-9791433-B2
Publication Date
2017-10-17
Expiration Date
Abstract
The present invention is directed to a multi-organ-chip device comprising a base layer; an organ layer arranged on the base layer; an antra layer arranged on the organ layer; and an actuator layer; wherein the base layer is configured to provide a solid support for the further layers; the organ layer is configured to comprise a multiplicity of individual organ equivalents, each organ equivalent comprising one or more organ growth sections, each of the organ growth sections being configured to comprise an organoid cavity for housing at least one organoid of an organ and to comprise a micro-inlet and a micro-outlet for fluid communication between the organoid cavity of the organ growth section and a self-contained circulation system, wherein the organ layer comprises at least one organ equivalent configured to represent the organs lung, small intestine, spleen, pancreas, liver, kidney and bone marrow, respectively, and a self-contained circulation system configured to be in direct fluid communication with the organ growth sections of the organ layer via the micro inlets and outlets of the organ growth sections; the antra layer is configured to comprise a multiplicity of cavities and tubes arranged to be in fluid communication with selected organ equivalents or organ growth sections in order to allow for exchange of fluids between cavities and organ growth sections; and the actuator layer is configured to comprise a multiplicity of actuators arranged and configured to regulate a pressure force applied on a selected organ equivalent, the self-contained circulation system and/or part thereof.
Core Innovation
The invention provides a multi-organ-chip device with a layered architecture comprising a base layer, an organ layer arranged on the base layer, an organ-holder layer arranged on the organ layer, an antra layer arranged on the organ-holder layer, and an actuator layer arranged on the antra layer. The base layer provides solid support for the further layers, and the organ-holder layer is configured to seal and stabilize the organ layer and maintain fluid communications between the multiplicity of individual organ equivalents and the antra layer.
The organ layer comprises a multiplicity of individual organ equivalents, and each organ equivalent includes at least one organ growth section. Each organ growth section includes an organoid cavity for housing at least one organoid of an organ and a micro-inlet and a micro-outlet for fluid communication between the organoid cavity and a self-contained circulation system. The self-contained circulation system is in direct fluid communication with the organ growth sections via the micro-inlets and micro-outlets.
The organ layer includes at least one organ equivalent configured to represent lungs, small intestine, spleen, pancreas, liver, kidneys, and bone marrow, respectively. The antra layer comprises a multiplicity of cavities and tubes arranged to be in fluid communication with selected organ equivalents or organ growth sections, allowing for an exchange of fluids between cavities and organ growth sections, and the actuator layer comprises a multiplicity of actuators arranged and configured to regulate a pressure force applicable on a selected organ equivalent and the self-contained circulation system.
Claims Coverage
The document includes one independent claim. Its coverage centers on a layered multi-organ-chip architecture, organ equivalents with organoid cavities and micro-inlets/outlets connected to a self-contained circulation system, an antra layer for fluid exchange, an organ-holder layer for sealing and stabilization, and an actuator layer for regulating pressure force.
Layered multi-organ-chip architecture with staged functional layers
A multi-organ-chip device comprising a base layer; an organ layer arranged on the base layer; an organ-holder layer arranged on the organ layer; an antra layer arranged on the organ-holder layer; and an actuator layer arranged on the antra layer, wherein the base layer provides solid support for the further layers.
Organoid-equipped organ equivalents connected to a self-contained circulation system
An organ layer comprising a multiplicity of individual organ equivalents, each organ equivalent comprising at least one organ growth section including an organoid cavity for housing at least one organoid of an organ, and a micro-inlet and a micro-outlet for fluid communication between the organoid cavity and a self-contained circulation system, with at least one organ equivalent configured to represent lungs, small intestine, spleen, pancreas, liver, kidneys, and bone marrow respectively; and the self-contained circulation system configured to be in direct fluid communication with the organ growth sections via the micro-inlets and micro-outlets.
Antra-layer cavities and tubes enabling fluid exchange
An antra layer comprising a multiplicity of cavities and tubes arranged to be in fluid communication with selected organ equivalents or organ growth sections allowing for an exchange of fluids between cavities and organ growth sections.
Organ-holder sealing and stabilized fluid communications
The organ-holder layer configured to seal and stabilize the organ layer and maintain fluid communications between the multiplicity of individual organ equivalents and the antra layer.
Actuator-layer pressure force regulation for selected organ equivalents and circulation system
An actuator layer comprising a multiplicity of actuators arranged and configured to regulate a pressure force applicable on a selected organ equivalent and the self-contained circulation system.
Overall claim coverage is directed to a stacked multi-organ-chip device where an organ layer containing multiple organ equivalents with organoid cavities is fluidly coupled to a self-contained circulation system, an antra layer provides additional fluid-exchange cavities and tubes, an organ-holder layer seals and stabilizes the organ layer, and an actuator layer uses multiple actuators to regulate pressure force on a selected organ equivalent and the circulation system.
Stated Advantages
Documented Applications
Long-term homeostatic culture and applications in safety testing and disease modeling.
Feasibility support for the circulation component by integrating an EC-lined pulsatile microvascular circuit, including shear stress characterization, imaging, and viability.
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