Microfluidic Cis-Co-Culture for Patient-Specific Cancer Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional systems for analyzing patient cancer samples fail to accurately mimic in vivo conditions, requiring large amounts of biological material, relying on population averages rather than single-cell data, and often use artificial enrichment of specific cell types, which reduces the similarity to the in vivo environment.
Innovation Solution
A microfluidic system that allows for cis-co-culture of target cancer cells with stromal cells from the same patient, maintaining them in a fluidic milieu without physical mingling, to replicate the in vivo environment more accurately and assess the response to pharmaceutical agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional in vitro models are used to analyze cancer cells, then the analysis can be performed with standard methods, but the models do not accurately mimic in vivo conditions because they lack neighboring cells, extracellular matrix, and systemic factors
Solution Approach 1:
The device is divided into multiple chambers separated by porous membranes, with each chamber housing different cell types (cancer cells, stromal cells, immune cells) that can interact through the membrane pores. This segmentation allows recreation of the complex in vivo microenvironment while maintaining controlled conditions for each cell type
Solution Approach 2:
The patent implements a hierarchical structure where chambers are nested within a larger device architecture, with porous membranes providing multiple levels of interaction. Cells are nested in specific spatial arrangements that mimic tissue organization, allowing simultaneous presence of multiple cell types and extracellular matrix components
2Measurement precision
If conventional functional cell assays are used, then population average data can be obtained, but single-cell data and valuable heterogeneity information are lost
Solution Approach 1:
The device partitions cells into individual chambers or micro-compartments, enabling single-cell or small-population analysis while maintaining high throughput through parallel processing of multiple chambers. Each chamber can be independently analyzed, preserving single-cell resolution data
Solution Approach 2:
The system enables transition from population-level measurements to single-cell measurements by changing the scale of analysis. Microfluidic channels and chambers are designed to manipulate and analyze individual cells or small cell groups, providing high-resolution data on cellular heterogeneity
3Quantity of substance
If artificial enrichment of specific cell types is used in co-culture systems, then the desired cell population can be obtained, but the similarity to the in vivo environment is reduced
Solution Approach 1:
Different chambers or regions of the device have specialized functions with locally optimized cell densities. Target cell types can be enriched in specific chambers while maintaining physiological ratios in other regions, allowing both quantity and fidelity requirements to be met simultaneously
Solution Approach 2:
The device segments different cell types into separate chambers that are physically separated but functionally connected through porous membranes. This allows artificial enrichment of specific cell types in certain chambers without disrupting the overall physiological microenvironment across the entire system
4Reliability
If large amounts of biological starting material are required for conventional assays, then sufficient statistical power can be achieved, but samples from some patients are insufficient
Solution Approach 1:
The device divides the sample into multiple small chambers, each containing a limited number of cells. By distributing patient material across many parallel chambers, the system achieves sufficient statistical power through high-throughput parallel analysis while requiring minimal total input material from each patient
Solution Approach 2:
The system performs multiple partial analyses in parallel across numerous chambers rather than requiring one large-scale analysis. This approach achieves comprehensive statistical power through cumulative data from many small experiments, reducing the burden on individual patient samples
Data Source
AI summary
The invention relates to systems and methods for studying patient cancer samples in cis-co-culture with stromal cells from the same patient. For example, the invention provide systems and methods for testing therapeutic agents in vitro in an environment that simulates an in vivo environment to identify agents that are therapeutically effective for the patient.