In Vitro Tissue Plate With Fluidic Channel For Vascularization

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Solution Overview

Problem

Current methods for testing therapeutic options for neurological disorders are hindered by the complexity of brain architecture and the blood-brain barrier, leading to unreliable animal tests and unrepresentative miniaturized organ-on-chip devices that are costly and incompatible with existing lab equipment.

Innovation Solution

An in vitro tissue plate system with a well plate, fluidic plate, and media manifold that allows for nutrient delivery and waste removal, promoting vascularization and mimicking natural tissue environments, compatible with existing lab equipment and capable of scalable testing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If animal studies are used to test therapeutic options for neurological disorders, then the studies can be performed with existing infrastructure, but the development cycles are long and the results have limited applicability to human use

Engineering Contradiction:
Improveapplicability to human useVSAvoiddevelopment cycles
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent creates human brain tissue copies in vitro using patient-specific induced pluripotent stem cells (iPSCs) to form organoids that replicate human brain architecture and blood-brain barrier function. These in vitro models provide human-relevant data without requiring animal studies, directly improving reliability while reducing development time through parallel testing capabilities

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent segments the brain tissue into discrete organoid units that can be individually cultured, manipulated, and tested in high-throughput formats. This segmentation enables parallel testing of multiple therapeutic compounds across multiple organoid replicates simultaneously, dramatically reducing development cycles while maintaining human relevance

Inventive Principle:
Principle #1Segmentation

2Productivity

If miniaturized organ-on-chip devices are used to model body structures, then the scale is reduced for testing, but the devices become unrepresentative of human body structures and incompatible with existing lab equipment

Engineering Contradiction:
Improvetesting speedVSAvoidrepresentativeness of human tissue
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent changes the size parameter of the tissue models from miniaturized chip-scale (unrepresentative) to human-relevant scale organoids (representative). The organoids are cultured to achieve human-tissue-equivalent dimensions and architectural complexity, allowing them to be tested with existing laboratory equipment while providing human-relevant results

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates accurate copies of human brain tissue architecture at human-relevant scales using patient-specific iPSCs. These organoid copies replicate the complex 3D structure, cell types, and blood-brain barrier function of human brain tissue, making them representative models that work with conventional laboratory infrastructure

Inventive Principle:
Principle #26Copying

3Reliability

If complex brain architecture and blood-brain barrier are modeled accurately, then the testing reliability improves, but the device complexity and cost increase

Engineering Contradiction:
Improvetesting accuracyVSAvoidmodel complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs self-organizing properties of stem cells to automatically form complex brain tissue architectures and blood-brain barrier structures without external manipulation. The iPSCs spontaneously differentiate and self-organize into organoid structures with authentic human tissue complexity, eliminating the need for complex engineering solutions while maintaining high testing reliability

Inventive Principle:
Principle #25Self-service

4Reliability

If human-relevant scale tissue models are used, then the results are more applicable to human use, but the cost of testing increases

Engineering Contradiction:
Improvehuman applicabilityVSAvoidtesting cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent segments the testing system into standardized, modular organoid units that can be produced in high-throughput formats. This segmentation enables parallel production and testing of multiple organoid replicates, distributing the cost across many testable units and reducing the per-experiment cost while maintaining human-relevant scale and reliability

Inventive Principle:
Principle #1Segmentation

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 reliable and rapid testing of therapeutic compounds at human-relevant scales, reducing the risk of failed human trials and facilitating cost-effective deployment in existing laboratories.

Implementation Method 1

a fluid channel extending between and fluidly connected to the tissue well and the waste well

Methodology Applied
Scientific EffectFluid flow:

Data Source

PatentUS11767498B2In vitro tissue plate
Publication Date: 2023.09.26 MASSACHUSETTS INST OF TECH
  • US11767498B2 patent drawing
  • US11767498B2 patent drawing
  • US11767498B2 patent drawing

AI summary

An in vitro tissue plate may include a well plate, a fluidic plate disposed on a bottom surface of the well plate, and a media manifold disposed on a bottom surface of the fluidic plate. The well plate may have at least two wells, including a tissue well and a waste well. The fluid plate may include a fluid channel extending between and fluidly connecting the tissue well to the waste well. The media manifold may include a one or more media outlets fluidly connected to the fluid channel. A tissue layer may be deposited in the tissue well. The tissue layer may include human cells such as neurovascular cells.