Microfluidic Tissue Culture Automation With TEER Verification
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Solution Overview
Problem
The implementation of microphysiological systems using 3D cell culture models requires high technical expertise and generates variations in test results due to user skill differences, making it difficult to inject cells into microfluidic chips and maintain consistent conditions.
Innovation Solution
An apparatus that automates the entire process of forming a microphysiological system, including a microfluidic device, culture unit, injection unit, perfusion unit, and resistance measurement unit, capable of injecting cells and culture medium, maintaining constant gas concentration and temperature, and measuring electrical resistance to verify tissue barrier formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If 3D cell culture models are implemented on microfluidic chips to closely mimic in vivo conditions, then the ability to study molecular-based tissue functions and directional growth is improved, but the technical expertise required and variation in test results increase
Solution Approach 1:
The system divides the complex 3D cell culture process into discrete automated modules: cell injection unit, ECM injection unit, culture medium circulation unit, and TEER measurement unit. Each module handles a specific step independently, reducing the technical barrier while maintaining the capability to study complex tissue functions.
Solution Approach 2:
The automated system performs all critical operations autonomously without requiring manual intervention. The microfluidic chip self-regulates fluid flow, the system automatically injects cells and ECM, and continuously monitors TEER values, eliminating the need for high user skill while preserving research capability.
2Manufacturing precision
If extracellular matrix is used in 3D cell culture to enable directional growth, then tissue morphology is improved, but shear stress increases making cell injection difficult
Solution Approach 1:
The system pre-preps cells and extracellular matrix in separate reservoirs before the culture process begins. The automated injection system then delivers these pre-prepared materials into the microfluidic chip through controlled fluid flow, avoiding the need for manual manipulation of viscous materials and reducing shear stress-related injection difficulties.
Solution Approach 2:
The system uses pressure-driven microfluidic flow to automatically inject cells and extracellular matrix into the chip. This hydraulic approach replaces manual injection techniques, providing controlled, low-shear stress delivery of materials while maintaining the ability to form proper 3D tissue structures.
3Adaptability or versatility
If manual cell injection techniques are used, then flexibility is maintained, but test result variation due to user skill differences increases
Solution Approach 1:
The system incorporates real-time TEER (transepithelial electrical resistance) measurement that provides feedback on tissue barrier formation. This automated feedback mechanism ensures consistent results by objectively monitoring culture progress, eliminating variability introduced by different users' manual injection skills while maintaining operational flexibility.
Solution Approach 2:
The system replaces manual mechanical injection operations with an automated microfluidic-based injection system. This substitution eliminates human skill variation from the process while maintaining the ability to adapt injection parameters, thereby improving test result consistency without sacrificing flexibility.
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 apparatus ensures consistent and automated formation and verification of microphysiological structures, enhancing user convenience and minimizing variations in test results.
Implementation Method 1
U.S. Patent Publication Nos. 20200332240 and 20210024866, and U.S. Patent Nos. 11597899 and 10519410, all of Emulate, describe a technique for perfusing a culture medium at a constant flow rate through a microfluidic chip using pressure generated by a pump
Implementation Method 2
describe a technique for perfusing a culture medium at a constant flow rate through a microfluidic chip using pressure generated by a pump
Implementation Method 3
a resistance measurement device (transepithelial/transendothelial electrical resistance, TEER) for verifying the formation of the MPS
Implementation Method 4
a gas concentration and temperature control device for creating an environment suitable for cell culture
Data Source
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AI summary
The present invention relates to an apparatus for forming a microphysiological system, including: a cabinet; a culture unit; an injection unit; a perfusion unit; and a resistance measurement unit. Specifically, in the microphysiological system of the present invention, the culture unit has a microfluidic device mounted thereon and inverts the microfluidic device, the injection unit is positioned at an upper end of the culture unit to supply cells and culture medium to the microfluidic device, the perfusion unit is positioned adjacent to the upper end of the culture unit to generate perfusion into an internal channel of the microfluidic device at a constant flow rate, and the resistance measurement unit is positioned at upper and lower ends of the culture unit to measure the resistance between upper and lower channels of the microfluidic device.