Perfusable Vascular Tissue Platform for Immune Infiltration Imaging
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Solution Overview
Problem
Current microfluidic platforms for vascularized tissues do not adequately mimic in vivo perfusability, limit imaging depth, and fail to model immune cell interactions and infiltration, making them unsuitable for studying vascular-related diseases and cancer.
Innovation Solution
Development of microfluidic devices with perfusable vascular networks and empty wells for easy integration of cells, spheroids, and ex vivo tissues, allowing lateral transport of molecules and cells, and enabling real-time imaging and drug screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional 2D cell culture or simple 3D spheroid models are used, then the system is simple and easy to manufacture, but it cannot accurately mimic the microphysiological function and three-dimensional microstructure of human organs
Solution Approach 1:
The microfluidic device is divided into multiple functional channels: a gel channel containing the 3D tissue construct, two media channels for perfusion, and phase guides for fluid separation. This segmentation allows each component to perform its specific function while collectively achieving accurate organ microstructure mimicry.
Solution Approach 2:
The gel channel is positioned between two media channels, creating a nested structure where the 3D tissue construct is surrounded by perfusable vascular networks. This nested arrangement enables the tissue to be embedded within a functional vascular system while maintaining spatial organization for accurate structural mimicry.
2Reliability
If a perfusable vascular network is constructed to supply nutrients and oxygen, then the tissue viability and microphysiological function are improved, but the device complexity and manufacturing difficulty increase
Solution Approach 1:
The microfluidic channels and phase guides are pre-fabricated using standard microfabrication techniques before the gel channel is populated with cells and extracellular matrix. This preliminary construction of the vascular network infrastructure enables subsequent easy population of the gel channel while ensuring reliable nutrient and oxygen supply.
Solution Approach 2:
Phase guides are introduced as intermediary structures between the gel channel and media channels to direct fluid flow and maintain separation. These intermediaries simplify the overall manufacturing process by providing clear fluid pathways while ensuring reliable perfusion of the 3D tissue construct.
3Manufacturing precision
If the vascular network is designed with specific barrier function to mimic in vivo conditions, then the biological accuracy is improved, but the device complexity increases
Solution Approach 1:
The gel channel is designed with specific local properties including extracellular matrix composition, porosity, and gelation conditions that create a barrier function matching the target organ. This localized optimization of material properties achieves biological accuracy without requiring complex overall device structure.
Solution Approach 2:
The vascular network's barrier function is achieved by controlling parameters such as gel concentration, cell density, and extracellular matrix composition within the gel channel. By adjusting these parameters, the system mimics in vivo barrier properties while maintaining a relatively simple device architecture.
4Manufacturing precision
If 3D structures such as organoids and ex vivo tissues are integrated into the microfluidic system, then the physiological representation is improved, but the ease of operation and sample integration becomes more difficult
Solution Approach 1:
The gel channel is prepared with pre-placed holes or cavities at predetermined locations before cell seeding. This preliminary preparation creates ready-to-receive spaces for organoids and ex vivo tissues, making sample integration straightforward while maintaining accurate physiological representation.
Solution Approach 2:
The device includes separate media channels and perfusion pathways that are independent from the gel channel containing the 3D tissue construct. This segmentation allows easy addition and removal of samples from the gel channel while maintaining the functional vascular network in the media channels.
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
Facilitates the formation of perfusable vascularized tissues with infiltrates, supporting immunotherapy drug screening and detailed imaging of molecular and cellular interactions, enhancing the study of vascular-related diseases and cancer.
Implementation Method 1
at least one gel channel (20) having a port (10) on a top surface (24), the gel channel (20) filled with a gel solution
Implementation Method 2
allowing lateral transport of molecules and cells
Data Source
AI summary
Microfluidic devices with open ports and gel channels for forming perfusable hydrogel vascular networks with holes or ports for samples, and methods of making and using, are provided which integrate interstitial flows to an ex vivo vascularized tissue model. Samples of cells, spheroids, organoids, and tissues can be used for screening of agents for efficacy, toxicity and dosage. The devices create interstitial flow from the top of the gel hole, through the sample toward the vascular networks, and/or luminal flows generated by a pressure difference between two media channels across the vascular network. This system is useful for studying angiogenesis, immune cell migration and testing new immunotherapy drug candidates.