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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Microdissected "cuboids" for microfluidic drug testing of intact tissues
Lisa F Horowitz1, Adan D Rodriguez, Allan Au-Yeung
1Department of Bioengineering, University of Washington, Seattle, WA, USA. lisafh@uw.edu.
Lab on a Chip
|November 11, 2020
Summary
New microfluidic platforms enable drug testing on human tissue "cuboids." This approach aims to improve drug discovery by providing more accurate preclinical results than animal models, advancing personalized medicine.
Area of Science:
- Biotechnology
- Drug Discovery
- Microfluidics
Background:
- Preclinical animal testing frequently fails to predict human drug responses, leading to high drug development failure rates.
- There is a critical need for functional drug testing platforms utilizing intact human tissues to enhance preclinical studies.
- Current methods lack the precision for multiplexed drug delivery to small tissue samples.
Purpose of the Study:
- To develop a microfluidic platform for selective drug treatment of microdissected human tissue samples.
- To enable high-throughput drug screening using uniformly sized tissue cuboids.
- To improve the accuracy of drug efficacy prediction in preclinical settings.
Main Methods:
- Developed a semi-automated method using a tissue chopper to create uniformly sized tissue cuboids.
- Designed a multi-well microfluidic platform with hydrodynamic traps to immobilize cuboids.
- Validated the platform using mouse liver and human glioma xenografts, assessing viability and microenvironment preservation.
- Utilized fluid dynamics simulations for platform design optimization.
- Demonstrated proof-of-concept with model compounds like dyes and cisplatin.
Main Results:
- Successfully generated uniformly sized tissue cuboids from mouse liver and human glioma xenografts.
- Demonstrated preservation of tissue microenvironment and cell viability after culture.
- Validated the microfluidic platform's ability to immobilize cuboids and deliver model compounds.
- Confirmed the utility of size uniformity for reducing assay heterogeneity and enabling automation.
Conclusions:
- The developed microfluidic platform and microdissection method offer a promising approach for functional drug testing on intact human tissues.
- High-throughput testing of human tissues could significantly impact drug discovery and accelerate personalized medicine.
- This platform complements animal studies by providing more predictive preclinical data.
