Microfluidic chip to model multi-organ interactions
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Solution Overview
Problem
Existing animal models struggle to accurately model inter-organ communication, particularly brain-lymph node interactions in neuroinflammation and neurodegeneration, due to challenges in isolating organ communication, analyzing internal organ functions over time, and species differences.
Innovation Solution
A microfluidic device with pumps, wells, and channels is used to model multi-organ interactions, allowing for the co-culture of tissue-engineered models of the brain, meningeal lymphatics, and lymph node paracortex under distinct media loops, mimicking physiological and pathological conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If animal models are used to study inter-organ communication, then biological mechanisms can be determined and drug efficacy tested, but species differences arise and communication between specific organ subsets cannot be isolated
Solution Approach 1:
The patent creates in vitro copies of human organs (brain, lymph node, meningeal lymphatics) using human-derived cells and tissues in a microfluidic system. This allows direct modeling of human inter-organ communication without relying on animal models, thereby eliminating species differences while maintaining biological relevance and enabling accurate study of human-specific physiological and pathological processes
Solution Approach 2:
The patent segments the complex animal model system into discrete, isolated organ modules that can be independently cultured and manipulated. By creating separate but connected chambers for each organ type in the microfluidic device, the system enables selective study of specific organ communication pathways without the confounding factors present in whole-animal models
2Measurement precision
If traditional animal models are used, then drug efficacy can be tested, but challenges arise in analyzing functions of internal organs such as the brain over time
Solution Approach 1:
The patent extracts the brain and other organs from the complex animal model system and places them in isolated but connected microfluidic chambers. This extraction allows direct access to organ cultures, enabling researchers to monitor and analyze organ function over time through media sampling and imaging without the anatomical barriers and complexity of whole-animal models
Solution Approach 2:
The patent introduces a microfluidic system with controlled media flow as an intermediary between the organ cultures and the researcher. This intermediary allows precise delivery of nutrients and removal of waste products while enabling continuous monitoring of organ function through the fluid medium, simplifying the complexity of direct organ analysis
3Ease of operation
If in vivo models are used to study brain-lymph node communication, then physiological conditions can be observed, but challenges arise in isolating communication between specific organs due to multiple barriers
Solution Approach 1:
The patent segments the communication pathway into discrete steps by creating separate chambers for each organ connected through controlled microfluidic channels. This segmentation allows the meningeal lymphatic barrier to be studied as a distinct, isolated component rather than one of many barriers in the complex in vivo system, greatly simplifying the ability to study specific organ communication pathways
Solution Approach 2:
The patent extracts the meningeal lymphatic barrier from the complex in vivo system and places it in an isolated microfluidic chamber where it can be studied in detail. This extraction removes the confounding factors of other physiological barriers present in vivo, allowing direct study of brain-lymph node communication through the meningeal route without interference from other pathways
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 study of communication between organs in a controlled, user-friendly, and cost-effective manner, predicting species-specific and individual responses, and facilitating the modeling of diseases like Alzheimer's and brain cancer.
Implementation Method 1
a first pump configured to pump a first fluid flowing through the microfluidic chip via a first channel
Data Source
AI summary
The present disclosure provides for devices, systems, and methods of using microfluidic chips to model multi-organ interactions. The microfluidic chip includes a first pump configured to pump a first fluid flowing through the microfluidic chip via a first channel and a second pump configured to pump a second fluid flowing through the microfluidic chip via a second channel. The microfluidic chip further includes a barrier well, including a barrier cell culture insert disposed in the barrier well. Additionally, the microfluidic chip includes the first channel connecting the first pump to a first barrier inlet and connecting a first barrier outlet to the first pump and the second channel connecting the second pump to a second barrier inlet and connecting a second barrier outlet to the second pump.