Lung-on-chip with integrated flexible barrier for cyclic strain
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Solution Overview
Problem
Current lung microphysiological systems, particularly those using PDMS, are limited by complex and costly fabrication processes, inability to model cyclic radial strain, and restricted three-dimensional architectures, which hinder their ability to accurately recapitulate the human lung microenvironment for preclinical trials.
Innovation Solution
A lung microphysiological system featuring a body with integrated microfluidic channels and a flexible barrier, where a culturing membrane composed of extracellular matrix proteins like collagen and elastin is subjected to cyclic radial strain and shear forces through vacuum and fluid flow, mimicking the alveolar-capillary barrier's mechanical forces, and fabricated using SLA, MSLA, and DLP 3D printing for reduced complexity and cost.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PDMS is used to fabricate lung microphysiological systems, then dynamic mechanical forces can be applied to model lung function, but the fabrication process becomes complex and costly
Solution Approach 1:
The patent combines the culturing membrane, vacuum channels, and circulation channel into a single integrated body fabricated from one piece of transparent sheet material. This merging eliminates the need for separate PDMS components and complex assembly steps, directly resolving the contradiction between modeling reliability and fabrication complexity.
Solution Approach 2:
The patent changes the material parameter from PDMS to transparent sheet material (such as PET, PC, or PMMA) that can be fabricated using simpler techniques like laser cutting or waterjet cutting. This parameter change maintains the ability to apply dynamic mechanical forces while dramatically simplifying the fabrication process.
2Ease of manufacture
If conventional in-vitro cell culture is used, then cell studies are simple, but the models cannot capture dynamic mechanical forces or cyclic strain
Solution Approach 1:
The patent introduces dynamic vacuum channels that can be activated to apply cyclic strain to the culturing membrane, transforming the static conventional cell culture into a dynamic system that replicates native lung mechanical forces while maintaining ease of operation through simple vacuum activation.
Solution Approach 2:
The patent uses a flexible culturing membrane made of transparent sheet material that can deform under vacuum to apply cyclic strain to cells, combining the simplicity of conventional culture with the physiological relevance of dynamic mechanical loading.
3Reliability
If animal models are used, then complex pathology information can be obtained, but they are costly and time-consuming to maintain
Solution Approach 1:
The patent creates a simplified in-vitro copy of the lung microenvironment using transparent sheet material and integrated microfluidic channels that replicate essential lung mechanical forces. This copy provides sufficient pathology modeling capability without the high costs and time requirements of animal models.
4Device complexity
If integrated fabrication is used, then device complexity is reduced, but manufacturing precision must be maintained
Solution Approach 1:
The patent segments the device into distinct functional regions (culturing membrane area, vacuum channels, circulation channel) that are all fabricated from one piece of material. This segmentation with unified fabrication maintains precision through the inherent accuracy of laser or waterjet cutting while keeping the overall process simple.
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
This approach enables a more accurate and cost-effective modeling of the lung microenvironment, capable of simulating the dynamic mechanical forces experienced in the human lung, thereby improving the development of therapies for respiratory diseases.
Implementation Method 1
providing a vacuum to the one or more vacuum channels causes the flexible barrier to deflect and in turn causes a pressure differential between the vacuum channel and the circulation channel
Implementation Method 2
a flexible barrier. The body and each flexible barrier may be integrally formed as a single, contiguous material
Implementation Method 3
Shear forces may be imparted to the culturing membrane by flowing cell media or other fluid through the circulation channel
Data Source
AI summary
Disclosed are microphysiological systems (MPS) that may be used to model microenvironments of the human lung. The system includes a body, having one or more vacuum channels and a circulation channel separated by one or more flexible barriers. An aperture exposes the circulation channel to the top surface of the body, over which a culturing membrane, having epithelial and endothelial cells, may be placed. The cells of the culturing membrane may be subjected to radial strain and shear forces by causing a fluid to flow through the circulation channel and applying a vacuum to the one or more vacuum channels, causing the one or more flexible barriers and the culturing membrane to deflect.