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Published on: February 11, 2019
A Microfluidic Droplet Array System for Cell-Based Drug Combination Screening
Guan-Sheng Du1,2,3, Jian-Zhang Pan1, Shi-Ping Zhao1
1Department of Chemistry, Institute of Microanalytical Systems, Zhejiang University, Hangzhou, China.
Abstract:
In the last few decades, drug combination therapy has been widely applied in oncology and in other complex diseases. Due to its potential advantage of lower drug toxicity and higher therapeutic efficacy, drug combination treatment has been more and more studied in fundamental labs and pharmacy companies. In this chapter, we report cell-based drug combination screening using a microfluidic droplet system based on a sequential operation droplet array (SODA) technique. In this system, an oil-covered two-dimensional droplet array chip was used as the platform for cell culture and analysis. This chip was fixed in an x-y-z translation stage under control of a computer program. A tapered capillary connected with a syringe pump was coupled with the droplet array chip to achieve multiple droplet manipulations including liquid metering, aspirating, depositing, mixing, and transferring. Complex multistep operations for drug combination screening involving long-term cell culture, medium changing, schedule-dependent drug dosage and stimulation, and cell viability testing were achieved in parallel using the present system. The drug consumption for each screening test was substantially decreased to 5 ng-5 μg, corresponding to 10- to 1000-fold reductions compared with traditional drug screening systems with 96- or 384-well plates.
Insights
This study introduces a microfluidic droplet system for cell-based drug combination screening. The novel Sequential Operation Droplet Array (SODA) technique significantly reduces drug consumption for enhanced oncology and complex disease research.
Area of Science:
- Biotechnology
- Oncology
- Pharmacology
Background:
- Drug combination therapy is increasingly vital for treating complex diseases like cancer.
- Traditional screening methods face challenges in efficiency and drug consumption.
Purpose of the Study:
- To develop and demonstrate a microfluidic droplet system for efficient cell-based drug combination screening.
- To enable complex, long-term cell culture and drug testing with reduced reagent usage.
Main Methods:
- Utilized a microfluidic droplet system employing the Sequential Operation Droplet Array (SODA) technique.
- Integrated a 2D droplet array chip with an x-y-z translation stage and capillary-based liquid handling for automated operations.
- Performed complex multistep operations including cell culture, medium changes, drug dosing, and viability testing in parallel.
Main Results:
- Achieved substantial reduction in drug consumption per screening test (5 ng–5 μg), representing a 10- to 1000-fold decrease compared to traditional plate-based methods.
- Successfully executed complex, schedule-dependent drug screening and long-term cell culture within the microfluidic system.
- Demonstrated parallel processing capabilities for high-throughput drug combination screening.
Conclusions:
- The SODA microfluidic system offers a powerful and efficient platform for cell-based drug combination screening.
- This technology significantly reduces drug usage, making it a cost-effective and scalable approach for pharmaceutical research and development.
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