Segmented Microfluidic Kidney-on-Chip for Renal Transporter Prediction
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Solution Overview
Problem
Current cell-based models fail to predict renal transporter activity and are not scalable for clinical outcomes due to in vitro-in vivo discrepancies, necessitating new methods to assess renal transporter-based drug-drug interactions and drug-associated kidney toxicities.
Innovation Solution
Microfluidic kidney on-chips, such as human Proximal Tubule-Kidney-Chip, Glomerulus (Kidney)-Chip, and Collecting Duct (Kidney)-Chip, are developed with a membrane separating proximal tubule cells and endothelial cells, allowing for continuous media flow and simulating kidney functions to measure transporter biomarkers, drug transport, and renal clearance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional cell-based models are used for drug testing, then the testing process is simple and inexpensive, but the models fail to predict renal transporter activity and show in vitro-in vivo discrepancies
Solution Approach 1:
The kidney device is segmented into distinct functional modules: a glomerulus module with endothelial cells and podocytes for filtration, and proximal tubule modules with epithelial cells for reabsorption and secretion. This segmentation allows each module to independently simulate specific kidney functions, improving predictive accuracy while maintaining manageable complexity through modular design
Solution Approach 2:
Different cell types are placed in specific locations to create functionally distinct zones: glomerular endothelial cells and podocytes in the filtration zone, proximal tubule epithelial cells in the reabsorption/secretion zones. Each location has optimized flow conditions and media composition tailored to the specific physiological requirements of that kidney segment, enhancing local functional accuracy
2Productivity
If traditional cell-based models are used, then the setup is simple, but the models are not scalable to predictive clinical outcomes
Solution Approach 1:
The microfluidic kidney on-chip platform is designed as a universal system that can test multiple drugs, evaluate various drug-drug interactions, and assess different kidney toxicity endpoints using the same device architecture. The modular design allows the same platform to simulate different kidney functions (filtration, reabsorption, secretion) and can be applied across diverse clinical research scenarios, enabling scalability without proportionally increasing complexity
Solution Approach 2:
The device employs a nested structure where the glomerulus module (with endothelial cells and podocytes) is integrated within the larger proximal tubule module framework. This nesting allows the filtration function to be embedded within the broader reabsorption and secretion functions, creating a compact yet comprehensive kidney model that scales efficiently
3Reliability
If simple cell cultures are used, then the experimentation is easy to conduct, but they cannot assess drug-drug interactions and kidney toxicities effectively
Solution Approach 1:
Multiple cell types (glomerular endothelial cells, podocytes, and proximal tubule epithelial cells) are merged into a single integrated microfluidic device that operates as a unified system. This combination allows the device to simultaneously perform filtration, reabsorption, and secretion functions, enabling comprehensive assessment of drug-drug interactions and kidney toxicities while maintaining a single operational platform that simplifies experimental conduct
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
These microfluidic devices effectively predict renal transporter functions and drug interactions, providing insights into kidney disease treatment and personalized medicine by mimicking in vivo kidney environments and improving predictive accuracy.
Implementation Method 1
said membrane contains pores (which allows for fluidic communication)
Data Source
AI summary
The present invention relates to microfluidic fluidic devices, methods and systems as microfluidic kidney on-chips, e.g. human Proximal Tubule-Kidney-Chip, Glomerulus (Kidney)-Chip, Collecting Duct (Kidney)-Chip. Devices, methods and systems are described for drug testing including drug transport and renal clearance. Further, such devices, methods and systems are used for determining drug-drug interactions and their effect upon renal transporter functions. Importantly, they may be used for pre-clinical and clinical drug development for treating kidney diseases and for personalized medicine.