Microfluidic Tissue Trapping with Suction and Bubble Traps

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Solution Overview

Problem

Current technologies fail to effectively recapitulate the tissue microenvironment and interactions between mammalian tissue samples and the host immune system, limiting the ability to observe dynamic processes and evaluate therapeutic compound responses in a physiologically relevant manner.

Innovation Solution

A microfluidic device with innovative tissue trapping geometries, such as heart-shaped branching structures, ribbed channels, and suction ports, that capture and maintain tissue samples in a flow field, allowing controlled exposure to fluid samples containing cells or therapeutic compounds, while preventing bubble interference and ensuring precise control over flow rates and shear forces.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional tissue culture methods are used, then tissue samples can be maintained, but the ability to recapitulate tissue microenvironment and immune system interactions is lost

Engineering Contradiction:

Improveability to recapitulate tissue microenvironmentVSAvoidphysiologically relevant interaction simulation

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The device segments the tissue sample into a controlled microenvironment within the microfluidic chip, separating it from conventional culture conditions while maintaining viability. The tissue is positioned in a specific region where it interacts with flowing fluid containing immune cells, creating a segmented but controlled physiological environment that recapitulates in vivo conditions.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The microfluidic device acts as an intermediary system between the tissue sample and the immune cell-containing fluid. It mediates their interaction by controlling fluid flow, maintaining appropriate shear forces, and enabling direct contact between tissue and immune cells while preventing contamination and maintaining physiological relevance.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If tissue samples are exposed to flowing fluid, then interaction with immune cells is enabled, but bubble interference occurs

Engineering Contradiction:

Improveimmune cell interaction capabilityVSAvoidbubble interference

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The device incorporates a bubble trap that converts the harmful effect of bubbles into a beneficial filtering mechanism. Bubbles that form during fluid introduction or flow are captured and removed by the trap, preventing them from interfering with tissue-immune cell interactions while allowing the continuous flow necessary for immune cell delivery.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Productivity

If high flow rates are used, then immune cell delivery is efficient, but shear forces damage tissue samples

Engineering Contradiction:

Improveimmune cell delivery efficiencyVSAvoidtissue sample integrity

Core Design Contradiction:

ProductivityVSStrength

Solution Approach 1:

The device utilizes parameter changes in fluid flow, specifically varying flow rates across different regions of the microfluidic chip. Higher flow rates are used in regions for efficient immune cell delivery, while lower flow rates are maintained at the tissue interface to minimize shear stress. The system dynamically adjusts flow parameters to optimize both cell delivery and tissue preservation.

Inventive Principle:

Principle #35Parameter changes

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 robust, high-throughput simulation of tissue interactions with cells and therapeutic compounds, maintaining tissue viability for extended periods, and optimizing the cross-section of interaction between tissue samples and fluid components, facilitating informed decision-making for immunotherapy treatments.

Implementation Method 1

one or more suction channels downstream of the one or more tissue traps and configured to hold the tissue sample in place within the one or more tissue traps

Methodology Applied

Scientific EffectSuction: Suction

Implementation Method 2

introducing a tissue sample into a first end of an inlet channel of a microfluidic device. The method can include introducing a fluid sample into the first end of the inlet channel to cause the tissue sample to flow to a tissue trapping region

Methodology Applied

Scientific EffectFluid flow transport: Advection

Data Source

PatentUS11852626B2Microfluidic tissue biopsy and immune response drug evaluation devices and systems

Publication Date: 2023.12.26 THE CHARLES STARK DRAPER LABORATORY INC

AI summary

This disclosure describes microfluidic tissue biopsy and immune response drug evaluation devices and systems. A microfluidic device can include an inlet channel having a first end configured to receive a fluid sample optionally containing a tissue sample. The microfluidic device can also include a tissue trapping region at the second end of the inlet channel downstream from the first end. The tissue trapping region can include one or more tissue traps configured to catch a tissue sample flowing through the inlet channel such that the fluid sample contacts the tissue trap. The microfluidic device can also include one or more channels providing an outlet.