Modular Organ Microphysiological System Pneumatic Fluid Control
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Solution Overview
Problem
Current multi-organ microphysiological systems (MPS) face challenges in accurately predicting human drug responses due to incomplete understanding of inter-tissue communication, limited pharmacokinetic studies, and hardware limitations such as fluid-surface interactions, adsorption of drugs and growth factors, and poor control over fluid directionality and recirculation, leading to inefficiencies in drug testing and biomarker discovery.
Innovation Solution
A multi-well cell culture system with integrated pumping, spontaneous liquid leveling, and programmable drug/media dosing, featuring a pneumatic plate for pressure and vacuum control, apical flow modules for microbial metabolites introduction, and capacitive fluid level sensing for precise fluid management, enabling robust and scalable non-contact fluid level detection and long-term culture of functional organ-like tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional microfluidic chips with closed format are used, then small fluid volumes can be operated, but fluid-surface interactions cause drug and growth factor adsorption
Solution Approach 1:
The patent extracts the culture wells from the closed microfluidic chip format and places them in an open multi-well plate format. This allows the culture medium to be exposed to air rather than being contained in closed channels, eliminating the fluid-surface interactions that cause drug and growth factor adsorption to channel walls.
Solution Approach 2:
The patent creates a multi-well plate system that replicates the functionality of microfluidic chips but uses a different physical format. The multi-well plate with integrated pumping system provides similar culture capabilities without the harmful adsorption effects of closed microfluidic channels.
2Ease of operation
If integrated pumping systems are implemented, then fluid directionality and recirculation can be controlled, but device complexity increases
Solution Approach 1:
The patent divides the system into modular components: a multi-well plate with individual wells, separate pumping modules, and integrated fluid paths. Each well can be independently controlled, and the pumping system is segmented into discrete units that can be added or removed based on experimental needs.
Solution Approach 2:
The integrated pumping system is designed to serve multiple functions: controlling fluid directionality between wells, maintaining recirculation within wells, and enabling programmable drug/media dosing. This multi-functional approach consolidates several control capabilities into a single system rather than requiring separate mechanisms for each function.
3Duration of action of stationary object
If extended culture periods are supported, then long-term organ tissue development is enabled, but contamination risk increases
Solution Approach 1:
The patent introduces an apical flow module that serves as an intermediary between the external environment and the culture wells. This module allows controlled introduction of microbial metabolites and sterile media while maintaining a barrier that prevents contamination during extended culture periods.
Solution Approach 2:
The system incorporates integrated pumping and fluid management that automatically maintains sterile conditions throughout extended culture periods. The programmable dosing system and controlled fluid flow eliminate the need for manual intervention, reducing contamination risk while supporting long-term culture.
4Measurement precision
If precise fluid level control is implemented, then pharmacokinetic studies are improved, but measurement and control complexity increases
Solution Approach 1:
The patent replaces complex mechanical fluid level sensing mechanisms with capacitive sensing technology. Capacitive sensors detect fluid levels through electrical field changes, providing precise measurement without moving parts or complex mechanical structures. This substitution maintains measurement precision while significantly reducing system complexity.
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
The system enhances the predictive power of preclinical assays by maintaining precise control over fluid levels and flow rates, supporting extended culture periods and accurate monitoring of microbial density, thereby improving the reliability and scalability of multi-organ interactions and drug testing.
Implementation Method 1
capacitive fluid level sensing for precise fluid management, enabling robust and scalable non-contact fluid level detection
Implementation Method 2
pneumatic plate for pressure and vacuum control
Implementation Method 3
pneumatic plate for pressure and vacuum control
Implementation Method 4
spontaneous liquid leveling
Data Source
Figure 1
Figure 2~3A
Figure 3B
AI summary
Fluidic multiwell bioreactors are provided as a microphysiological platform for in vitro investigation of multi-organ crosstalks with microbiome for an extended period of time of at least weeks and months. The platform has one or more improvements over existing bioreactors, including on-board pumping for pneumatically driven fluid flow, a redesigned spillway for self- leveling from source to sink, a non-contact built-in fluid level sensing device, precise control on fluid flow profile and partitioning, and facile reconfigurations such as daisy chaining and multilayer stacking. The platform supports the culture of multiple organs together with microbiome in a microphysiological, interacted systems, suitable for a wide range of biomedical applications including systemic toxicity studies and physiology- based pharmacokinetic and pharmacodynamic predictions. A process to fabricate the bioreactors is also provided.