Parallel Microfluidic Bioreactor Networks for Circadian Media Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current bioreactor systems lack the capability to operate large arrays of isolated or coupled organ chips, bioreactors, and chemostats with the necessary fluidic control and parallelism, limiting their ability to simulate physiologically realistic circadian rhythms and time-dependent drug concentrations, and they are not scalable to thousands of channels.
Innovation Solution
A fluidic system with a distribution and sampling network, featuring multichannel pumps and valves for parallel operation of multiple bioreactors and chemostats, allowing for continuous media perfusion, sampling, and analysis, with a systemic circulation and mixing reservoir, and a network of pumps and valves for independent control of each module.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional bioreactor systems are used to operate multiple bioreactors and chemostats, then the capability to simulate physiologically realistic circadian rhythms and time-dependent drug concentrations is improved, but the scalability to thousands of channels and fluidic control parallelism deteriorates
Solution Approach 1:
The system divides the bioreactor array into multiple groups, with each group served by its own dedicated pump. This segmentation allows the system to scale to thousands of channels by adding more pump groups while maintaining the complex fluidic control needed for circadian rhythm simulation and time-dependent drug concentration delivery.
Solution Approach 2:
The pump control system is designed to universally manage multiple pumps, each capable of performing the same complex functions of simulating circadian rhythms and time-dependent drug concentrations. This multi-functionality enables scalable operation where each additional pump group can independently handle the same physiological simulation requirements.
2Adaptability or versatility
If traditional fluidic control systems are used for multiple bioreactors, then the operation of isolated or coupled organ chips and bioreactors is enabled, but the fluidic control parallelism and system scalability deteriorates
Solution Approach 1:
The fluidic control system is segmented into multiple independent pump control units, each managing a specific group of bioreactors and chemostats. This segmentation provides the necessary fluidic control parallelism while keeping each control unit's complexity manageable, enabling the system to operate both isolated and coupled organ chips and bioreactors.
Solution Approach 2:
The system introduces intermediary fluidic components and control mechanisms that mediate between the pump control system and the bioreactor array. These intermediaries enable complex fluidic operations for isolated or coupled organ chips while maintaining overall system parallelism and scalability.
3Measurement precision
If batch culture with media replacement every 24 hours is used, then the concentration changes at the end of each period are maximized, but the continuous changes in nutrient and metabolite concentrations affect reaction kinetics and cellular gene expression
Solution Approach 1:
The system implements periodic action through circadian rhythm simulation, where media composition and flow rates are modulated in 24-hour cycles that mimic natural physiological rhythms. This periodic action maintains concentration changes at the end of each period while stabilizing reaction kinetics and cellular gene expression through rhythm-synchronized nutrient and metabolite fluctuations.
Solution Approach 2:
The system dynamically changes media parameters (composition, flow rate, concentration) in a controlled manner to maintain stable reaction kinetics and cellular gene expression. By adjusting parameters periodically to match circadian rhythms, the system achieves both measurable concentration changes and kinetic stability.
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 simultaneous operation and analysis of multiple bioreactors and chemostats, providing a stable and interpretable environment for cell culture, capable of mimicking in vivo conditions and allowing for real-time sampling and analysis, thereby accelerating biological research and drug discovery.
Implementation Method 1
a first pump fluidically coupled between the systemic circulation and mixing reservoir and the fluid distribution network for withdrawing media from the systemic circulation and mixing reservoir and delivering the media to the fluid distribution network
Implementation Method 2
a second pump fluidically coupled between the fluid collection and sampling network and a sample vial for withdrawing effluent of the plurality of fluidic modules from the fluid collection and sampling network and delivering the effluent to one or more sample vials
Implementation Method 3
a systemic circulation and mixing reservoir
Data Source
AI summary
A fluidic system includes a fluid distribution network, and a fluid collection and sampling network; a plurality of fluidic modules fluidically coupled between the fluid distribution network and the fluid collection and sampling network in parallel; a systemic circulation and mixing reservoir; and a first pump, and a second pump, wherein the first pump is fluidically coupled between the systemic circulation and mixing reservoir and the fluid distribution network for withdrawing media from the systemic circulation and mixing reservoir and delivering the media to the fluid distribution network; and wherein the second pump is fluidically coupled between the fluid collection and sampling network and a sample vial for withdrawing effluent of the plurality of fluidic modules from the fluid collection and sampling network and delivering the effluent to one or more sample vials.