Construction of multiple concentration gradients for single-cell level drug screening

This paper presents a novel microfluidic device for single-cell drug screening that overcomes limitations of previous methods by incorporating a multi-concentration gradient generator. A Tai Chi-spiral mixer within the generator rapidly creates linear concentration gradients. The device was used to study the effects of 5-fluorouracil and cisplatin, individually and in combination, on human hepatoma and breast carcinoma cells. Results showed that both drugs inhibited cancer cell growth, with a synergistic effect observed for human hepatoma cells. The study also explored the correlation between cell biomechanics (deformability and size) and drug resistance, revealing that smaller and more deformable cells exhibited higher resistance. The device offers a simple, reliable platform for optimizing drug dosages and screening both single-agent and combination therapies at the single-cell level.

Shaofei Shen, Fangjuan Zhang, Yali Zhang, Yi Li, Yanbing Niu, Long Pang, Jinyi Wang