Related Experiment Video
Updated: Apr 26, 2026
Generation of Dynamical Environmental Conditions using a High-Throughput Microfluidic Device
Published on: April 17, 2021
A spatiotemporally defined in vitro microenvironment for controllable signal delivery and drug screening
Ching-Te Kuo1, Hao-Kai Liu, Guan-Syuan Huang
1Institute of Applied Mechanics, National Taiwan University, Taipei, Taiwan, Republic of China. andrew@iam.ntu.edu.tw.
Abstract:
Cancer metastasis and drug resistance are important malignant tumor phenotypes that cause roughly 90% mortality in human cancers. Current therapeutic strategies, however, face substantial challenges partially due to a lack of applicable pre-clinical models and drug-screening platforms. Notably, microscale and three-dimensional (3D) tissue culture platforms capable of mimicking in vivo microenvironments to replicate physiological conditions have become vital tools in a wide range of cellular and clinical studies. Here, we present a microfluidic device capable of mimicking a configurable tumor microenvironment to study in vivo-like cancer cell migration as well as screening of inhibitors on both parental tumors and migratory cells. In addition, a novel evaporation-based paper pump was demonstrated to achieve adaptable and sustainable concentration gradients for up to 6 days in this model. This straightforward modeling approach allows for fast patterning of a wide variety of cell types in 3D and may be further integrated into biological assays. We also demonstrated cell migration from tumor spheroids induced by an epidermal growth factor (EGF) gradient and exhibited lowered expression of an epithelial marker (EpCAM) compared with parental cells, indicative of partial epithelial-mesenchymal transition (EMT) in this process. Importantly, pseudopodia protrusions from the migratory cells - critical during cancer metastasis - were demonstrated. Insights gained from this work offer new opportunities to achieve active control of in vitro tumor microenvironments on-demand, and may be amenable towards tailored clinical applications.
Insights
This study introduces a microfluidic device that models tumor microenvironments for cancer metastasis and drug resistance research. The platform enables in vivo-like cell migration studies and inhibitor screening, advancing pre-clinical cancer models.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Microfluidics
Background:
- Cancer metastasis and drug resistance are major causes of cancer mortality, yet effective pre-clinical models are lacking.
- Microscale, 3D tissue culture platforms are crucial for replicating in vivo conditions in cancer research.
- Current therapeutic strategies face challenges due to limitations in existing pre-clinical models and drug-screening platforms.
Purpose of the Study:
- To develop a microfluidic device that mimics a configurable tumor microenvironment for studying cancer cell migration.
- To establish a platform for screening drug inhibitors on both primary tumors and migratory cancer cells.
- To investigate cancer cell migration and epithelial-mesenchymal transition (EMT) in a controlled in vitro setting.
Main Methods:
- Development of a microfluidic device for creating 3D cell cultures.
- Integration of an evaporation-based paper pump for sustained concentration gradients.
- Induction of cell migration using epidermal growth factor (EGF) gradients and analysis of epithelial marker (EpCAM) expression.
Main Results:
- Demonstrated in vivo-like cancer cell migration from tumor spheroids in a microfluidic device.
- Observed reduced EpCAM expression in migratory cells, indicating partial epithelial-mesenchymal transition (EMT).
- Visualized pseudopodia protrusions, essential for cancer metastasis, in migratory cells.
Conclusions:
- The microfluidic device provides a configurable tumor microenvironment for studying metastasis and drug resistance.
- This platform facilitates the screening of inhibitors and offers insights into cancer cell migration dynamics.
- The model is adaptable for various cell types and may be integrated into future biological assays and clinical applications.
