Rapid Microfluidic Drug Sensitivity Testing Within 5 Days Using Minimal Clinical Tumor Samples

TL;DR

A new microfluidic system enables rapid drug sensitivity testing using small tumor samples within 5 days, preserving tumor heterogeneity and avoiding cell expansion.

Contribution

The novel air-punched fabrication approach enables high-throughput drug testing with minimal clinical samples in just 5 days.

Findings

The microfluidic system allows rapid formation and 3D culture of tumor cell spheroids from small clinical samples.

Drug sensitivity testing was successfully performed on primary samples from 21 breast cancer patients within 5 days.

The system supports both mono-drug and combination-drug testing without the need for cell pre-expansion.

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.

This study develops the air‐punched fabrication approach for 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 high‐throughput drug sensitivity testing can be achieved within 5 days. The system is applied in rapid, high‐throughput drug sensitivity testing on primary cell samples from 21 clinical breast cancer patients to quantify the responses to chemotherapy drugs and endocrine drugs.

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