Multiwell Microfluidic Model for Dynamic Tumor-Immune Perfusion
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Solution Overview
Problem
Evaluating the efficacy of candidate immunotherapies against diseases such as cancer is challenging due to difficulties in mimicking the in vitro microenvironment in which the immunotherapy is to be introduced, particularly in facilitating interactions between immunotherapies and tissue samples in a laboratory setting.
Innovation Solution
A microfluidic device with a multiwell plate that mimics the tumor-immune microenvironment, featuring bilayer or single-layer microenvironment units with mechanical trapping features and micropumps, allowing for the perfusion of tissue samples with candidate immunotherapies and independent control of perfusion rates across units, enabling simultaneous evaluation of multiple immunotherapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional in vitro methods are used to evaluate immunotherapies, then the evaluation process is simple to perform, but the ability to mimic the actual microenvironment and facilitate interactions between immunotherapies and tissue samples is poor
Solution Approach 1:
The device is divided into multiple independent microenvironment units (96 wells), each capable of housing tissue samples and facilitating immunotherapy interactions separately. This segmentation allows parallel evaluation while maintaining individual microenvironment control, resolving the contradiction between reliability through realistic microenvironment mimicry and complexity by using standardized modular units.
Solution Approach 2:
A hydrogel matrix is introduced as an intermediary substance within each microenvironment unit to mimic the extracellular matrix and facilitate realistic interactions between immunotherapies and tissue samples. This hydrogel intermediary provides the necessary microenvironmental cues without requiring complex living tissue structures, thereby improving reliability while managing device complexity.
2Productivity
If multiple immunotherapies are evaluated sequentially in separate experiments, then each evaluation can be performed thoroughly, but the time and resources required increase significantly
Solution Approach 1:
Multiple microenvironment units are combined into a single integrated device platform with shared control systems. Each unit can independently evaluate different immunotherapies simultaneously, merging 96 separate evaluation capabilities into one device. This resolves the contradiction by enabling parallel productivity while using a unified control architecture rather than 96 separate systems.
Solution Approach 2:
The device is designed with universal components that can handle multiple immunotherapy evaluations through a single control system. The micropump array and fluidic network provide multi-functional capabilities to deliver different immunotherapies to different microenvironment units simultaneously, achieving high productivity without proportionally increasing control system complexity.
3Reliability
If tissue samples are perfused with candidate immunotherapies in static conditions, then the setup is simple, but the interaction dynamics between immunotherapies and tissue samples are not accurately captured
Solution Approach 1:
The system transitions from static perfusion to dynamic flow-based perfusion using individually controllable micropumps for each microenvironment unit. This allows regulation of flow rates and perfusion dynamics to match in vivo conditions, improving interaction evaluation accuracy while using standardized pump components to manage system complexity.
Solution Approach 2:
The perfusion system enables independent adjustment of flow rate parameters for each microenvironment unit, allowing optimization of immunotherapy-tissue sample interactions under different dynamic conditions. This parameter control improves reliability by capturing realistic interaction dynamics while using a modular pump architecture to prevent exponential complexity growth.
Data Source
AI summary
A microfluidic device for modeling a tumor-immune microenvironment can include a multiwell plate defining a plurality of microenvironment units fluidically coupled with a plurality of wells. Each microenvironment unit of the plurality of microenvironment units can include one or more compartments. Each microenvironment unit can include a trapping feature positioned within the one or more compartments. The trapping feature can be defined by a portion of at least one of a sidewall or a floor of the one or more compartments. The trapping feature can restrict movement of a tissue sample introduced into the one or more compartments and to allow fluid to flow past the tissue sample. The microfluidic device can include a plurality of micropumps each coupled with a respective well and configured to control movement of a respective fluid sample through each respective well.