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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Rapid Microfluidic Drug Sensitivity Testing Within 5 Days Using Minimal Clinical Tumor Samples
Yi-Xue Chen1, Yi Zhang2,3,4, Yu-Jie Yan3
1Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China.
Abstract:
Rapid screening of personalized drugs based on patients' primary cell samples can provide precise and timely treatment guidance for clinical oncology patients. However, this goal faces great challenges due to the scarce clinical samples and large sample consumption, and long experimental time required by current drug screening methods. Here, a rapid, high-throughput microfluidic drug sensitivity testing system capable of accomplishing single and combination drug screening of multiple antitumor drugs in 5 days is established with minimal amounts of clinical primary tumor samples, avoiding the need for cell pre-expansion and preserving the tumor heterogeneity. An airflow-impacting approach is developed to fabricate nanoliter-scale microcavity arrays with ultra-smooth microcavity surfaces, with which rapid formation and 3D culture of tumor cell spheroids from small numbers of cell samples, as well as the subsequent high-throughput drug sensitivity testing can be achieved within 5 days. This applies the system in rapid drug sensitivity testing on primary samples from 21 clinical breast cancer patients to quantify the responses of patient-derived cells to chemotherapy and endocrine drugs under both the mono-drug and combinational-drug treatment modes.
Insights
This study presents a rapid microfluidic system for personalized cancer drug screening using minimal patient samples. The innovative technology enables faster, more accurate treatment decisions for oncology patients within five days.
Area of Science:
- Biomedical Engineering
- Oncology
- Microfluidics
Background:
- Current drug screening methods for clinical oncology patients are hindered by scarce samples, high consumption, and long experimental times.
- Personalized medicine requires rapid drug sensitivity testing on patient-derived cells to guide treatment effectively.
Purpose of the Study:
- To develop a rapid, high-throughput microfluidic system for personalized drug sensitivity testing using minimal clinical samples.
- To enable single and combination drug screening for multiple antitumor drugs within five days.
Main Methods:
- Fabrication of nanoliter-scale microcavity arrays using an airflow-impacting approach for ultra-smooth surfaces.
- Rapid formation and 3D culture of tumor cell spheroids from small cell samples.
- High-throughput drug sensitivity testing on patient-derived cells within five days.
Main Results:
- A microfluidic system was established for rapid drug sensitivity testing, requiring minimal patient samples and avoiding cell pre-expansion.
- The system successfully screened single and combination drug responses in primary samples from 21 breast cancer patients.
- Tumor heterogeneity was preserved, and responses to chemotherapy and endocrine drugs were quantified.
Conclusions:
- The developed microfluidic system offers a rapid and efficient platform for personalized drug screening in oncology.
- This technology can significantly improve treatment guidance for cancer patients by providing timely drug response data.
- The system's ability to preserve tumor heterogeneity is crucial for accurate personalized treatment strategies.

