Microfluidic Blood-Urine Circuit for Homeostatic Microphysiological Systems
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Solution Overview
Problem
Current microfluidic devices lack the capability to maintain stable microenvironments over long periods and effectively emulate the physiological interactions of multiple organ functionalities, which is crucial for pharmacokinetic-pharmacodynamic analysis and ADME(T) profiling.
Innovation Solution
A novel microfluidic device with a 'blood' circuit and a 'urine' circuit, including a filtration unit and a reabsorption unit, connected via a filtration and reabsorption barrier, mimicking renal function, allowing for the emulation of human organ-to-organ crosstalk and systemic regulatory circuits, using induced pluripotent stem cell-derived organ-specific precursor cells or organoids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional static cell and tissue cultures are used, then the setup is simple, but the capability to emulate physiological interactions and maintain stable microenvironments over long periods is insufficient
Solution Approach 1:
The device is divided into multiple organ-on-a-chip modules (kidney, liver, intestine, lung, brain) that can be independently configured and connected. Each module maintains its own microenvironment while being integrated into a larger system, allowing stable conditions to be maintained in each compartment through separate control mechanisms.
Solution Approach 2:
Multiple organ modules are nested within a single microfluidic device platform, with each organ chip containing its own microenvironment. The kidney module itself contains nested filtration and reabsorption units, creating hierarchical structures that maintain stability at multiple levels simultaneously.
2Adaptability or versatility
If single organ microfluidic systems are used, then the device complexity is low, but the capability to emulate physiological interactions between multiple organs is insufficient
Solution Approach 1:
The microfluidic device platform is designed to accommodate multiple organ modules that can interact with each other through shared fluid pathways. The system can simulate various physiological scenarios involving one or multiple organs simultaneously, making it universally applicable for studying different organ interactions and systemic physiological conditions.
Solution Approach 2:
Multiple organ modules are combined within a single integrated device, allowing fluid and molecular exchange between different organs. The kidney, liver, intestine, lung, and brain modules can be connected through common microfluidic channels, enabling the emulation of systemic physiological interactions and disease states involving multiple organ systems.
3Duration of action of moving object
If long-term culture is implemented, then the duration of action increases, but the maintenance of stable microenvironment becomes more difficult
Solution Approach 1:
The device incorporates monitoring systems that track physiological parameters such as pH, oxygen levels, and metabolite concentrations in real-time. Based on this feedback, the microfluidic system can dynamically adjust fluid flow rates, composition, and other parameters to maintain stable microenvironments throughout long-term culture periods, preventing degradation of experimental conditions over time.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables the establishment of a stable microenvironment for pharmacokinetic-pharmacodynamic analysis and ADME(T) profiling, supporting long-term homeostasis and allowing for the assessment of drug interactions across multiple organ systems, enhancing the accuracy and reliability of drug testing.
Implementation Method 1
the filtration unit comprises a filtration barrier that selectively allows the passage of molecules from the first circuit to the second circuit based on size and charge of the molecules
Implementation Method 2
the reabsorption unit comprises a barrier that allows reabsorption of fluid from the second circuit to the first circuit
Data Source
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AI summary
The present disclosure relates to novel microfluidic devices and their use for operating microphysiological systems. The novel microfluidic devices are particularly useful for pharmacokinetic-pharmacodynamic analysis in the context of ADME(T) profiling. The present disclosure provides novel microfluidic devices comprising a first "blood" circuit with one or more cell culture compartments, and a second "urine" circuit comprising a renal filtration and reabsorption unit, wherein both circuits are connected with each other via the filtration unit and the reabsorption unit. The present disclosure further provides methods, kits and assays implementing the novel microfluidic devices.