A dual-functional microfluidic chip for guiding personalized lung cancer medicine: combining EGFR mutation detection and organoid-based drug response test

Kexin Zhang, Jiyu Xi, Huiting Zhao, Yadong Wang, Jianchao Xue, Naixin Liang*, Zewen Wei*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

3 引用 (Scopus)

摘要

Many efforts have been paid to advance the effectiveness of personalized medicine for lung cancer patients. Sequencing-based molecular diagnosis of EGFR mutations has been widely used to guide the selection of anti-lung-cancer drugs. Organoid-based assays have also been developed to ex vivo test individual responses to anti-lung-cancer drugs. After addressing several technical difficulties, a new combined strategy, in which anti-cancer medicines are first selected based on molecular diagnosis and then ex vivo tested on organoids, has been realized in a single dual-functional microfluidic chip. A DNA-based nanoruler has been developed to detect the existence of EGFR mutations and shrink the detection period from weeks to hours, compared with sequencing. The employment of the DNA-based nanoruler creates a possibility to purposively test anti-cancer drugs, either EGFR-TKIs or chemotherapy drugs, not both, on limited amounts of organoids. Moreover, a DNA-based nanosensor has been developed to recognize intracellular ATP variation without harming cell viability, realizing in situ monitoring of the whole course growth status of organoids for on-chip drug response test. The dual-functional microfluidic chip was validated by both cell lines and clinical samples from lung cancer patients. Furthermore, based on the dual-functional microfluidic chip, a fully automated system has been developed to span the divide between experimental procedures and therapeutic approaches. This study constitutes a novel way of combining EGFR mutation detection and organoid-based drug response test on an individual patient for guiding personalized lung cancer medicine.

源语言英语
页(从-至)1762-1774
页数13
期刊Lab on a Chip
24
6
DOI
出版状态已出版 - 14 2月 2024

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引用此

Zhang, K., Xi, J., Zhao, H., Wang, Y., Xue, J., Liang, N., & Wei, Z. (2024). A dual-functional microfluidic chip for guiding personalized lung cancer medicine: combining EGFR mutation detection and organoid-based drug response test. Lab on a Chip, 24(6), 1762-1774. https://doi.org/10.1039/d3lc00974b